Galanin: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
Information was added to the tissue distribution section and clinical characteristics section (including the new addiction, cognitive performance, depression, and pain and neuroprotection subsections). 10 new sources were also added
consistent citation formatting; combined repeated citations
Line 52: Line 52:


==Tissue distribution==
==Tissue distribution==
Galanin is located predominantly in the central nervous system and gastrointestinal tract. Within the central nervous system, highest concentrations are found in the [[hypothalamus]], with lower levels in the [[cerebral cortex|cortex]] and [[brainstem]]. In the hypothalamus, it is for example found in the [[ventrolateral preoptic nucleus]] where it has sleep-promoting function. Within the brain, galanin has also been found in the ventral forebrain and amygdala.<ref name=":6">{{Citation|last=Kuteeva|first=Eugenia|title=Galanin, Galanin Receptor Subtypes and Depression-Like Behaviour|date=2010|url=http://link.springer.com/10.1007/978-3-0346-0228-0_12|work=Galanin|volume=102|pages=163–181|editor-last=Hökfelt|editor-first=Tomas|publisher=Springer Basel|doi=10.1007/978-3-0346-0228-0_12|isbn=978-3-0346-0227-3|access-date=2020-03-03|last2=Hökfelt|first2=Tomas|last3=Wardi|first3=Tara|last4=Ögren|first4=Sven Ove}}</ref> Along with this, the immune reaction of galanin in the brain is centered in the hypothalamopituitary.<ref>{{Cite journal|last=Ch'ng|first=J. L. C.|last2=Christofides|first2=N. D.|last3=Anand|first3=P.|last4=Gibson|first4=S. J.|last5=Allen|first5=Y. S.|last6=Su|first6=H. C.|last7=Tatemoto|first7=K.|last8=Morrison|first8=J. F. B.|last9=Polak|first9=J. M.|last10=Bloom|first10=S. R.|date=1985-10-01|title=Distribution of galanin immunoreactivity in the central nervous system and the responses of galanin-containing neuronal pathways to injury|url=http://www.sciencedirect.com/science/article/pii/0306452285900077|journal=Neuroscience|language=en|volume=16|issue=2|pages=343–354|doi=10.1016/0306-4522(85)90007-7|issn=0306-4522}}</ref> Gastrointestinal galanin is most abundant in the [[duodenum]], with lower concentrations in the stomach, small intestine, and colon.<ref name="pmid2448788"/> Galanin is also expressed in the skin where is serves anti-inflammatory functions.<ref name=":2">{{Citation|last=Bauer|first=J. W.|title=Galanin Family of Peptides in Skin Function|date=2010|url=http://link.springer.com/10.1007/978-3-0346-0228-0_5|work=Galanin|volume=102|pages=51–59|editor-last=Hökfelt|editor-first=Tomas|publisher=Springer Basel|doi=10.1007/978-3-0346-0228-0_5|isbn=978-3-0346-0227-3|access-date=2020-01-30|last2=Lang|first2=R.|last3=Jakab|first3=M.|last4=Kofler|first4=B.}}</ref> Specifically, it has been found in keratinocytes, eccrine sweat glands, and around blood vessels.<ref name=":2" /> Galanin has been found in endocrine tumors.<ref name=":1">{{Citation|last=Mitsukawa|first=K.|title=Galanin, Galanin Receptors, and Drug Targets|date=2010|url=http://link.springer.com/10.1007/978-3-0346-0228-0_2|work=Galanin|volume=102|pages=7–23|editor-last=Hökfelt|editor-first=Tomas|publisher=Springer Basel|doi=10.1007/978-3-0346-0228-0_2|isbn=978-3-0346-0227-3|access-date=2020-01-30|last2=Lu|first2=X.|last3=Bartfai|first3=T.}}</ref> Within gastric cancer cells, galanin has been found to have a tumor suppressive role, but hypermethylation has been shown to stop its tumor suppressive properties.<ref>{{Cite journal|last=Yoon|first=Daseul|last2=Bae|first2=Kieun|last3=Lee|first3=Min-Kyeong|last4=Kim|first4=Jin Hee|last5=Yoon|first5=Kyong-Ah|date=2018-02-20|editor-last=Suzuki|editor-first=Hiromu|title=Galanin is an epigenetically silenced tumor suppressor gene in gastric cancer cells|url=http://dx.plos.org/10.1371/journal.pone.0193275|journal=PLOS ONE|language=en|volume=13|issue=2|pages=e0193275|doi=10.1371/journal.pone.0193275|issn=1932-6203|pmc=PMC5819827|pmid=29462183}}</ref>
Galanin is located predominantly in the central nervous system and gastrointestinal tract. Within the central nervous system, highest concentrations are found in the [[hypothalamus]], with lower levels in the [[cerebral cortex|cortex]] and [[brainstem]]. In the hypothalamus, it is for example found in the [[ventrolateral preoptic nucleus]] where it has sleep-promoting function. Within the brain, galanin has also been found in the ventral forebrain and amygdala.<ref name=":6">{{cite journal | vauthors = Kuteeva E, Hökfelt T, Wardi T, Ogren SO | title = Galanin, galanin receptor subtypes and depression-like behaviour | journal = Experientia Supplementum | volume = 102 | pages = 163–81 | date = 2010 | pmid = 21299068 | doi = 10.1007/978-3-0346-0228-0_12 | publisher = Springer Basel | isbn = 978-3-0346-0227-3 | veditors = Hökfelt T }}</ref> Along with this, the immune reaction of galanin in the brain is centered in the hypothalamopituitary.<ref>{{cite journal | vauthors = Ch'ng JL, Christofides ND, Anand P, Gibson SJ, Allen YS, Su HC, Tatemoto K, Morrison JF, Polak JM, Bloom SR | display-authors = 6 | title = Distribution of galanin immunoreactivity in the central nervous system and the responses of galanin-containing neuronal pathways to injury | journal = Neuroscience | volume = 16 | issue = 2 | pages = 343–54 | date = October 1985 | pmid = 2417156 | doi = 10.1016/0306-4522(85)90007-7 }}</ref> Gastrointestinal galanin is most abundant in the [[duodenum]], with lower concentrations in the stomach, small intestine, and colon.<ref name="pmid2448788"/> Galanin is also expressed in the skin where is serves anti-inflammatory functions.<ref name=":2">{{cite journal | vauthors = Bauer JW, Lang R, Jakab M, Kofler B | title = Galanin family of peptides in skin function | journal = Experientia Supplementum | volume = 102 | pages = 51–9 | date = 2010 | pmid = 21299061 | doi = 10.1007/978-3-0346-0228-0_5 | publisher = Springer Basel | isbn = 978-3-0346-0227-3 | veditors = Hökfelt T }}</ref> Specifically, it has been found in keratinocytes, eccrine sweat glands, and around blood vessels.<ref name=":2" /> Galanin has been found in endocrine tumors.<ref name="Mitsukawa_2010">{{cite journal | vauthors = Mitsukawa K, Lu X, Bartfai T | title = Galanin, galanin receptors, and drug targets | journal = Experientia Supplementum | volume = 102 | pages = 7–23 | date = 2010 | pmid = 21299058 | doi = 10.1007/978-3-0346-0228-0_2 | publisher = Springer Basel | isbn = 978-3-0346-0227-3 | veditors = Hökfelt T }}</ref> Within gastric cancer cells, galanin has been found to have a tumor suppressive role, but hypermethylation has been shown to stop its tumor suppressive properties.<ref>{{cite journal | vauthors = Yoon D, Bae K, Lee MK, Kim JH, Yoon KA | title = Galanin is an epigenetically silenced tumor suppressor gene in gastric cancer cells | journal = PloS One | volume = 13 | issue = 2 | pages = e0193275 | date = 2018-02-20 | pmid = 29462183 | pmc = 5819827 | doi = 10.1371/journal.pone.0193275 | veditors = Suzuki H }}</ref>


==Structure==
==Structure==
Line 128: Line 128:


===Appetite===
===Appetite===
Injections of galanin into the paraventricular nucleus (PVN) acutely stimulate food intake in rats.<ref name=Appetitezinc2007>{{cite journal |authors=Jing MY, Sun JY, Weng XY. |title=Insights on zinc regulation of food intake and macronutrient selection. |journal=Biol Trace Elem Res|date=2007 |pmid=17435261 |doi=10.1007/BF02686029}}</ref> Additionally, injections of galanin into the lateral ventricle of the hypothalamus creates the urge to feed, with a preference for eating fats. <ref name=":12">{{Citation|last=Mitsukawa|first=K.|title=Galanin, Galanin Receptors, and Drug Targets|date=2010|url=http://link.springer.com/10.1007/978-3-0346-0228-0_2|work=Galanin|volume=102|pages=7–23|editor-last=Hökfelt|editor-first=Tomas|publisher=Springer Basel|doi=10.1007/978-3-0346-0228-0_2|isbn=978-3-0346-0227-3|access-date=2020-01-30|last2=Lu|first2=X.|last3=Bartfai|first3=T.}}</ref> Galanin also regulates glucose metabolism and can potentially alleviate symptoms of Diabetes Type II due to its interaction with insulin resistance.<ref name=":3">{{Cite journal|last=Fang|first=Penghua|last2=Yu|first2=Mei|last3=Shi|first3=Mingyi|last4=Bo|first4=Ping|last5=Zhang|first5=Zhenwen|date=2019-11-06|title=Galanin peptide family regulation of glucose metabolism|url=http://www.sciencedirect.com/science/article/pii/S0091302219300615|journal=Frontiers in Neuroendocrinology|language=en|pages=100801|doi=10.1016/j.yfrne.2019.100801|issn=0091-3022}}</ref> Galanin is an inhibitor of pancreatic secretion of insulin.<ref name=":12" />
Injections of galanin into the paraventricular nucleus (PVN) acutely stimulate food intake in rats.<ref name=Appetitezinc2007>{{cite journal |authors=Jing MY, Sun JY, Weng XY. |title=Insights on zinc regulation of food intake and macronutrient selection. |journal=Biol Trace Elem Res|date=2007 |pmid=17435261 |doi=10.1007/BF02686029}}</ref> Additionally, injections of galanin into the lateral ventricle of the hypothalamus creates the urge to feed, with a preference for eating fats.<ref name="Mitsukawa_2010" /> Galanin also regulates glucose metabolism and can potentially alleviate symptoms of Diabetes Type II due to its interaction with insulin resistance.<ref name=":3">{{Cite journal|last=Fang|first=Penghua|last2=Yu|first2=Mei|last3=Shi|first3=Mingyi|last4=Bo|first4=Ping|last5=Zhang|first5=Zhenwen|date=2019-11-06|title=Galanin peptide family regulation of glucose metabolism|url=http://www.sciencedirect.com/science/article/pii/S0091302219300615|journal=Frontiers in Neuroendocrinology|language=en|pages=100801|doi=10.1016/j.yfrne.2019.100801|issn=0091-3022}}</ref> Galanin is an inhibitor of pancreatic secretion of insulin.<ref name="Mitsukawa_2010" />


=== Addiction ===
=== Addiction ===
Galanin plays a role in addiction regulation.<ref name=":0">{{Cite journal|last=Genders|first=Shannyn G.|last2=Scheller|first2=Karlene J.|last3=Djouma|first3=Elvan|date=2018-06-24|title=Neuropeptide modulation of addiction: Focus on galanin|url=http://www.sciencedirect.com/science/article/pii/S0149763418301404|journal=Neuroscience & Biobehavioral Reviews|language=en|doi=10.1016/j.neubiorev.2018.06.021|issn=0149-7634}}</ref> It is involved in repeated alcohol intake. <ref name=":13">{{Citation|last=Mitsukawa|first=K.|title=Galanin, Galanin Receptors, and Drug Targets|date=2010|url=http://link.springer.com/10.1007/978-3-0346-0228-0_2|work=Galanin|volume=102|pages=7–23|editor-last=Hökfelt|editor-first=Tomas|publisher=Springer Basel|doi=10.1007/978-3-0346-0228-0_2|isbn=978-3-0346-0227-3|access-date=2020-01-30|last2=Lu|first2=X.|last3=Bartfai|first3=T.}}</ref> Along with addiction to alcohol, galanin has been shown to play a role in addiction to nicotine and opiates.<ref name=":0" />
Galanin plays a role in addiction regulation.<ref name=":0">{{Cite journal|last=Genders|first=Shannyn G.|last2=Scheller|first2=Karlene J.|last3=Djouma|first3=Elvan|date=2018-06-24|title=Neuropeptide modulation of addiction: Focus on galanin|url=http://www.sciencedirect.com/science/article/pii/S0149763418301404|journal=Neuroscience & Biobehavioral Reviews|language=en|doi=10.1016/j.neubiorev.2018.06.021|issn=0149-7634}}</ref> It is involved in repeated alcohol intake.<ref name="Mitsukawa_2010" /> Along with addiction to alcohol, galanin has been shown to play a role in addiction to nicotine and opiates.<ref name=":0" />


===Alzheimer's disease===
===Alzheimer's disease===
Line 141: Line 141:


=== Cognitive Performance ===
=== Cognitive Performance ===
Galanin participates in cognitive performance and has been shown to weaken learning and cognition.<ref name=":14">{{Citation|last=Mitsukawa|first=K.|title=Galanin, Galanin Receptors, and Drug Targets|date=2010|url=http://link.springer.com/10.1007/978-3-0346-0228-0_2|work=Galanin|volume=102|pages=7–23|editor-last=Hökfelt|editor-first=Tomas|publisher=Springer Basel|doi=10.1007/978-3-0346-0228-0_2|isbn=978-3-0346-0227-3|access-date=2020-01-30|last2=Lu|first2=X.|last3=Bartfai|first3=T.}}</ref>
Galanin participates in cognitive performance and has been shown to weaken learning and cognition.<ref name="Mitsukawa_2010" />


=== Depression ===
=== Depression ===
Line 153: Line 153:


=== Pain and Neuroprotection ===
=== Pain and Neuroprotection ===
Galanin plays an inhibitory role in pain processing<ref name=":4">{{Citation|last=Hobson|first=S-A.|title=Galanin Acts as a Trophic Factor to the Central and Peripheral Nervous Systems|date=2010|url=http://link.springer.com/10.1007/978-3-0346-0228-0_3|work=Galanin|volume=102|pages=25–38|editor-last=Hökfelt|editor-first=Tomas|publisher=Springer Basel|doi=10.1007/978-3-0346-0228-0_3|isbn=978-3-0346-0227-3|access-date=2020-03-01|last2=Bacon|first2=A.|last3=Elliot-Hunt|first3=C. R.|last4=Holmes|first4=F. E.|last5=Kerr|first5=N. C. H.|last6=Pope|first6=R.|last7=Vanderplank|first7=P.|last8=Wynick|first8=D.}}</ref>, with high doses having been shown to reduce pain.<ref name=":15">{{Citation|last=Mitsukawa|first=K.|title=Galanin, Galanin Receptors, and Drug Targets|date=2010|url=http://link.springer.com/10.1007/978-3-0346-0228-0_2|work=Galanin|volume=102|pages=7–23|editor-last=Hökfelt|editor-first=Tomas|publisher=Springer Basel|doi=10.1007/978-3-0346-0228-0_2|isbn=978-3-0346-0227-3|access-date=2020-01-30|last2=Lu|first2=X.|last3=Bartfai|first3=T.}}</ref> When galanin is added to the spinal core, neuropathic pain is reduced.<ref name=":5">{{Citation|last=Xu|first=Xiao-Jun|title=Galanin and Spinal Pain Mechanisms: Past, Present, and Future|date=2010|url=http://link.springer.com/10.1007/978-3-0346-0228-0_4|work=Galanin|volume=102|pages=39–50|editor-last=Hökfelt|editor-first=Tomas|publisher=Springer Basel|doi=10.1007/978-3-0346-0228-0_4|isbn=978-3-0346-0227-3|access-date=2020-03-01|last2=Hökfelt|first2=Tomas|last3=Wiesenfeld-Hallin|first3=Zsuzsanna}}</ref> Along with this, galanin is believed to be effective in reducing spinal hyperexcitability.<ref name=":5" /> Sensory neurons increasingly release galanin when they are damaged.<ref name=":5" /> An increase in the concentrations of galanin are also believed to be for neuroprotective reasons and lead to promoted neurogenesis.<ref name=":15" /> GalR2 activation is believed to mediate the survival role galanin plays in the dorsal root ganglion<ref name=":4" />
Galanin plays an inhibitory role in pain processing<ref name=":4">{{Citation|last=Hobson|first=S-A.|title=Galanin Acts as a Trophic Factor to the Central and Peripheral Nervous Systems|date=2010|url=http://link.springer.com/10.1007/978-3-0346-0228-0_3|work=Galanin|volume=102|pages=25–38|editor-last=Hökfelt|editor-first=Tomas|publisher=Springer Basel|doi=10.1007/978-3-0346-0228-0_3|isbn=978-3-0346-0227-3|access-date=2020-03-01|last2=Bacon|first2=A.|last3=Elliot-Hunt|first3=C. R.|last4=Holmes|first4=F. E.|last5=Kerr|first5=N. C. H.|last6=Pope|first6=R.|last7=Vanderplank|first7=P.|last8=Wynick|first8=D.}}</ref>, with high doses having been shown to reduce pain.<ref name="Mitsukawa_2010" /> When galanin is added to the spinal core, neuropathic pain is reduced.<ref name=":5">{{Citation|last=Xu|first=Xiao-Jun|title=Galanin and Spinal Pain Mechanisms: Past, Present, and Future|date=2010|url=http://link.springer.com/10.1007/978-3-0346-0228-0_4|work=Galanin|volume=102|pages=39–50|editor-last=Hökfelt|editor-first=Tomas|publisher=Springer Basel|doi=10.1007/978-3-0346-0228-0_4|isbn=978-3-0346-0227-3|access-date=2020-03-01|last2=Hökfelt|first2=Tomas|last3=Wiesenfeld-Hallin|first3=Zsuzsanna}}</ref> Along with this, galanin is believed to be effective in reducing spinal hyperexcitability.<ref name=":5" /> Sensory neurons increasingly release galanin when they are damaged.<ref name=":5" /> An increase in the concentrations of galanin are also believed to be for neuroprotective reasons and lead to promoted neurogenesis.<ref name="Mitsukawa_2010" /> GalR2 activation is believed to mediate the survival role galanin plays in the dorsal root ganglion<ref name=":4" />


===Parental role in mice===
===Parental role in mice===

Revision as of 07:19, 4 April 2020

GAL
Identifiers
AliasesGAL, GAL-GMAP, GALN, GLNN, GMAP, ETL8, galanin and GMAP prepropeptide
External IDsOMIM: 137035; MGI: 95637; HomoloGene: 7724; GeneCards: GAL; OMA:GAL - orthologs
Orthologs
SpeciesHumanMouse
Entrez

51083

14419

Ensembl

ENSG00000069482

ENSMUSG00000024907

UniProt

P22466

P47212

RefSeq (mRNA)

NM_015973

NM_010253
NM_001329667

RefSeq (protein)

NP_057057

NP_001316596
NP_034383

Location (UCSC)Chr 11: 68.68 – 68.69 MbChr 19: 3.46 – 3.46 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
Galanin
Identifiers
CAS Number
ChemSpider
  • none
ChEMBL
Chemical and physical data
FormulaC146H213N43O40
Molar mass3210.56 g/mol g·mol−1
 ☒NcheckY (what is this?)  (verify)

Galanin is a neuropeptide encoded by the GAL gene,[5] that is widely expressed in the brain, spinal cord, and gut of humans as well as other mammals. Galanin signaling occurs through three G protein-coupled receptors.[6]

The functional role of galanin remains largely unknown; however, galanin is predominantly involved in the modulation and inhibition of action potentials in neurons. Galanin has been implicated in many biologically diverse functions, including: nociception, waking and sleep regulation, cognition, feeding, regulation of mood, regulation of blood pressure, it also has roles in development as well as acting as a trophic factor.[7] Galanin neurons in the medial preoptic area of the hypothalamus may govern parental behaviour.[8] Galanin is linked to a number of diseases including Alzheimer's disease, epilepsy as well as depression, eating disorders and cancer.[9][10] Galanin appears to have neuroprotective activity as its biosynthesis is increased 2-10 fold upon axotomy in the peripheral nervous system as well as when seizure activity occurs in the brain. It may also promote neurogenesis.[6]

Galanin is predominantly an inhibitory, hyperpolarizing neuropeptide[11] and as such inhibits neurotransmitter release. Galanin is often co-localized with classical neurotransmitters such as acetylcholine, serotonin, and norepinephrine, and also with other neuromodulators such as neuropeptide Y, substance P, and vasoactive intestinal peptide.[12]

Discovery

Galanin was first identified from porcine intestinal extracts in 1978 by Professor Viktor Mutt and colleagues at the Karolinska Institute, Sweden[13] using a chemical assay technique that detects peptides according to its C-terminal alanine amide structure. Galanin is so-called because it contains an N-terminal glycine residue and a C-terminal alanine.[14] The structure of galanin was determined in 1983 by the same team, and the cDNA of galanin was cloned from a rat anterior pituitary library in 1987.[13]

Tissue distribution

Galanin is located predominantly in the central nervous system and gastrointestinal tract. Within the central nervous system, highest concentrations are found in the hypothalamus, with lower levels in the cortex and brainstem. In the hypothalamus, it is for example found in the ventrolateral preoptic nucleus where it has sleep-promoting function. Within the brain, galanin has also been found in the ventral forebrain and amygdala.[15] Along with this, the immune reaction of galanin in the brain is centered in the hypothalamopituitary.[16] Gastrointestinal galanin is most abundant in the duodenum, with lower concentrations in the stomach, small intestine, and colon.[17] Galanin is also expressed in the skin where is serves anti-inflammatory functions.[18] Specifically, it has been found in keratinocytes, eccrine sweat glands, and around blood vessels.[18] Galanin has been found in endocrine tumors.[19] Within gastric cancer cells, galanin has been found to have a tumor suppressive role, but hypermethylation has been shown to stop its tumor suppressive properties.[20]

Structure

Endogenously occurring galanin sequences
Species 1 6 11 16 21 26 !
Pig G W T L N S A G Y L L G P H A I D N H R S F H D K Y G L A *
Human G W T L N S A G Y L L G P H A V G N H R S F S D K N G L T S **
Cow G W T L N S A G Y L L G P H A L D S H R S F Q D K H G L A *
Rat G W T L N S A G Y L L G P H A I D N H R S F S D K H G L T*
* C-terminal amide ** C-terminal free acid

Galanin is a peptide consisting of a chain of 29 amino acids (30 amino acids in humans) produced from the cleavage of a 123-amino acid protein known as prepro galanin, which is encoded by the GAL gene.[5] The sequence of this gene is highly conserved among mammals, showing over 85% homology between rat, mouse, porcine, bovine, and human sequences.[12] In these animal forms, the first 15 amino acids from the N-terminus are identical, but amino acids differ at several positions on the C-terminal end of the protein.

These slight differences in protein structure have far-reaching implications on their function. For example, porcine and rat galanin inhibit glucose-induced insulin secretion in rats and dogs but have no effect on insulin secretion in humans. This demonstrates that it is essential to study the effects of galanin and other regulatory peptides in their autologous species.[21]

The galanin family of protein consists of four proteins, of which GAL was the first to be identified. The second was galanin message-associated protein (GMAP), a 59- or 60-amino acid peptide also formed from the cleavage of prepro galanin.[14] The other two peptides, galanin-like peptide (GALP) and alarin, were identified relatively recently and are both encoded for in the same gene, the prepro GALP gene. GALP and alarin are produced by different post-transcriptional splicing of this gene.[22]

Galanin
Identifiers
SymbolGalanin
PfamPF01296
InterProIPR008174
PROSITEPDOC00673
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
Galanin message associated peptide (GMAP)
Identifiers
SymbolGMAP
PfamPF06540
InterProIPR013068
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

Receptors

Galanin signalling occurs through three classes of receptors, GALR1, GALR2, and GALR3, which are all part of the G protein-coupled receptor (GPCR) superfamily. Galanin receptors are expressed in the central nervous system, in the pancreas, and on solid tumours. The level of expression of the different receptors varies at each location, and this distribution changes after injury to neurons.[6] Experiments into the function of the receptor subtypes involve mostly genetic knockout mice. The location of the receptor and the combination of receptors that are inhibited or stimulated heavily affect the outcome of galanin signalling.[6]

Clinical characteristics

Appetite

Injections of galanin into the paraventricular nucleus (PVN) acutely stimulate food intake in rats.[23] Additionally, injections of galanin into the lateral ventricle of the hypothalamus creates the urge to feed, with a preference for eating fats.[19] Galanin also regulates glucose metabolism and can potentially alleviate symptoms of Diabetes Type II due to its interaction with insulin resistance.[24] Galanin is an inhibitor of pancreatic secretion of insulin.[19]

Addiction

Galanin plays a role in addiction regulation.[25] It is involved in repeated alcohol intake.[19] Along with addiction to alcohol, galanin has been shown to play a role in addiction to nicotine and opiates.[25]

Alzheimer's disease

One of the pathological features of the brain in the later stages of Alzheimer's disease is the presence of overgrown GAL-containing fibres innervating the surviving cholinergic neurons.[26] Another feature is an increase in the expression of GAL and GAL receptors, in which increases of up to 200% have been observed in postmortem brains of Alzheimer's patients.[6][22] The cause and role of this increase is poorly understood.[26][27]

It has been suggested that the hyper-innervation acts to promote the death of these neurons and that the inhibitory effect of galanin on cholinergic neurons worsened the degeneration of cognitive function in patients by decreasing the amount of acetylcholine available to these neurons.[6][26]

A second hypothesis has been generated based on data that suggest GAL is involved in protecting the hippocampus from excitotoxic damage and the neurons in the cholinergic basal forebrain from amyloid toxicity.[28]

Cognitive Performance

Galanin participates in cognitive performance and has been shown to weaken learning and cognition.[19]

Depression

Noradrenaline and serotonin, two neurotransmitters involved in depression, are both co-expressed and modulated by galanin, suggesting that galanin plays a role in the regulation of depression.[29] Stimulation of the Gal1 and Gal3 receptors result in depression-like behaviors, whereas stimulation of the Gal2 receptor results in reduced depression-like behaviors.[29] Currently, one of the potential mechanisms for this is that galanin stimulates the hypothalamus-pituitary-adrenal axis, which leads to an increase in glucocorticoid secretion.[29] Increased levels of glucocorticoid hormones is common in those who suffer from depression.[30]

Epilepsy

Galanin in the hippocampus is an inhibitor of glutamate but not of GABA. This means that galanin is capable of increasing the seizure threshold [6] and, therefore, is expected to act as an anticonvulsant. To be specific, GalR1 has been linked to the suppression of spontaneous seizures.[31][32] An agonist antiepileptic drug candidate is NAX 5055.[33][34]

In development

It has been shown that galanin plays a role in the control of the early post-natal neural development of the dorsal root ganglion (DRG).[13] Galanin-mutant animals show a 13% decrease in the number of adult DRG cells as well as a 24% decrease in the percentage of cells expressing substance P. This suggests that the cell loss by apoptosis that usually occurs in the developing DRG is regulated by galanin and that the absence of galanin results in an increase in the number of cells that die.

Pain and Neuroprotection

Galanin plays an inhibitory role in pain processing[35], with high doses having been shown to reduce pain.[19] When galanin is added to the spinal core, neuropathic pain is reduced.[36] Along with this, galanin is believed to be effective in reducing spinal hyperexcitability.[36] Sensory neurons increasingly release galanin when they are damaged.[36] An increase in the concentrations of galanin are also believed to be for neuroprotective reasons and lead to promoted neurogenesis.[19] GalR2 activation is believed to mediate the survival role galanin plays in the dorsal root ganglion[35]

Parental role in mice

A report has indicated that Galanin-expressing neurons in the medial preoptic area of the brain are responsible for regulating aggression towards pups by male mice.[8]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000069482 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024907 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b Evans H, Baumgartner M, Shine J, Herzog H (December 1993). "Genomic organization and localization of the gene encoding human preprogalanin". Genomics. 18 (3): 473–7. doi:10.1016/S0888-7543(11)80002-9. PMID 7508413.
  6. ^ a b c d e f g Mitsukawa K, Lu X, Bartfai T (June 2008). "Galanin, galanin receptors and drug targets". Cell. Mol. Life Sci. 65 (12): 1796–805. doi:10.1007/s00018-008-8153-8. PMID 18500647.
  7. ^ Mechenthaler I (June 2008). "Galanin and the neuroendocrine axes". Cell. Mol. Life Sci. 65 (12): 1826–35. doi:10.1007/s00018-008-8157-4. PMID 18500643.
  8. ^ a b Wu Z, Autry AE, Bergan JF, Watabe-Uchida M, Dulac CG (May 2014). "Galanin neurons in the medial preoptic area govern parental behaviour". Nature. 509 (7500): 325–30. doi:10.1038/nature13307. PMC 4105201. PMID 24828191.
  9. ^ Lundström L, Elmquist A, Bartfai T, Langel U (2005). "Galanin and its receptors in neurological disorders". Neuromolecular Med. 7 (1–2): 157–80. doi:10.1385/NMM:7:1-2:157. PMID 16052044.
  10. ^ Berger A, Santic R, Hauser-Kronberger C, Schilling FH, Kogner P, Ratschek M, Gamper A, Jones N, Sperl W, Kofler B (June 2005). "Galanin and galanin receptors in human cancers". Neuropeptides. 39 (3): 353–9. doi:10.1016/j.npep.2004.12.016. PMID 15944034.
  11. ^ Ito M (September 2009). "Functional roles of neuropeptides in cerebellar circuits". Neuroscience. 162 (3): 666–72. doi:10.1016/j.neuroscience.2009.01.019. PMID 19361475.
  12. ^ a b Bartfai T (2000). "Galanin – A neuropeptide with important central nervous system actions". Archived from the original on December 2, 2010. Retrieved November 19, 2009.
  13. ^ a b c Wynick D, Thompson SW, McMahon SB (February 2001). "The role of galanin as a multi-functional neuropeptide in the nervous system". Current Opinion in Pharmacology. 1 (1): 73–7. doi:10.1016/S1471-4892(01)00006-6. PMID 11712539.
  14. ^ a b Hökfelt T, Tatemoto K (June 2008). "Galanin--25 years with a multitalented neuropeptide". Cell. Mol. Life Sci. 65 (12): 1793–5. doi:10.1007/s00018-008-8152-9. PMID 18500648.
  15. ^ Kuteeva E, Hökfelt T, Wardi T, Ogren SO (2010). Hökfelt T (ed.). "Galanin, galanin receptor subtypes and depression-like behaviour". Experientia Supplementum. 102. Springer Basel: 163–81. doi:10.1007/978-3-0346-0228-0_12. ISBN 978-3-0346-0227-3. PMID 21299068.
  16. ^ Ch'ng JL, Christofides ND, Anand P, Gibson SJ, Allen YS, Su HC, et al. (October 1985). "Distribution of galanin immunoreactivity in the central nervous system and the responses of galanin-containing neuronal pathways to injury". Neuroscience. 16 (2): 343–54. doi:10.1016/0306-4522(85)90007-7. PMID 2417156.
  17. ^ Kaplan LM, Spindel ER, Isselbacher KJ, Chin WW (February 1988). "Tissue-specific expression of the rat galanin gene". Proc. Natl. Acad. Sci. U.S.A. 85 (4): 1065–9. doi:10.1073/pnas.85.4.1065. PMC 279702. PMID 2448788.
  18. ^ a b Bauer JW, Lang R, Jakab M, Kofler B (2010). Hökfelt T (ed.). "Galanin family of peptides in skin function". Experientia Supplementum. 102. Springer Basel: 51–9. doi:10.1007/978-3-0346-0228-0_5. ISBN 978-3-0346-0227-3. PMID 21299061.
  19. ^ a b c d e f g Mitsukawa K, Lu X, Bartfai T (2010). Hökfelt T (ed.). "Galanin, galanin receptors, and drug targets". Experientia Supplementum. 102. Springer Basel: 7–23. doi:10.1007/978-3-0346-0228-0_2. ISBN 978-3-0346-0227-3. PMID 21299058.
  20. ^ Yoon D, Bae K, Lee MK, Kim JH, Yoon KA (2018-02-20). Suzuki H (ed.). "Galanin is an epigenetically silenced tumor suppressor gene in gastric cancer cells". PloS One. 13 (2): e0193275. doi:10.1371/journal.pone.0193275. PMC 5819827. PMID 29462183.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  21. ^ Bersani M, Johnsen AH, Højrup P, Dunning BE, Andreasen JJ, Holst JJ (June 1991). "Human galanin: primary structure and identification of two molecular forms". FEBS Lett. 283 (2): 189–94. doi:10.1016/0014-5793(91)80585-Q. PMID 1710578.
  22. ^ a b Lang R, Gundlach AL, Kofler B (August 2007). "The galanin peptide family: receptor pharmacology, pleiotropic biological actions, and implications in health and disease". Pharmacol. Ther. 115 (2): 177–207. doi:10.1016/j.pharmthera.2007.05.009. PMID 17604107.
  23. ^ "Insights on zinc regulation of food intake and macronutrient selection". Biol Trace Elem Res. 2007. doi:10.1007/BF02686029. PMID 17435261. {{cite journal}}: Cite uses deprecated parameter |authors= (help)
  24. ^ Fang, Penghua; Yu, Mei; Shi, Mingyi; Bo, Ping; Zhang, Zhenwen (2019-11-06). "Galanin peptide family regulation of glucose metabolism". Frontiers in Neuroendocrinology: 100801. doi:10.1016/j.yfrne.2019.100801. ISSN 0091-3022.
  25. ^ a b Genders, Shannyn G.; Scheller, Karlene J.; Djouma, Elvan (2018-06-24). "Neuropeptide modulation of addiction: Focus on galanin". Neuroscience & Biobehavioral Reviews. doi:10.1016/j.neubiorev.2018.06.021. ISSN 0149-7634.
  26. ^ a b c Counts SE, Perez SE, Mufson EJ (June 2008). "Galanin in Alzheimer's disease: neuroinhibitory or neuroprotective?". Cell. Mol. Life Sci. 65 (12): 1842–53. doi:10.1007/s00018-008-8159-2. PMC 2911017. PMID 18500641.
  27. ^ Counts SE, Perez SE, Ginsberg SD, De Lacalle S, Mufson EJ (May 2003). "Galanin in Alzheimer disease". Mol. Interv. 3 (3): 137–56. doi:10.1124/mi.3.3.137. PMID 14993421.
  28. ^ Ding X, MacTavish D, Kar S, Jhamandas JH (February 2006). "Galanin attenuates beta-amyloid (Abeta) toxicity in rat cholinergic basal forebrain neurons". Neurobiol. Dis. 21 (2): 413–20. doi:10.1016/j.nbd.2005.08.016. PMID 16246567.
  29. ^ a b c Kuteeva, Eugenia; Hökfelt, Tomas; Wardi, Tara; Ögren, Sven Ove (2010), Hökfelt, Tomas (ed.), "Galanin, Galanin Receptor Subtypes and Depression-Like Behaviour", Galanin, vol. 102, Springer Basel, pp. 163–181, doi:10.1007/978-3-0346-0228-0_12, ISBN 978-3-0346-0227-3, retrieved 2020-03-03
  30. ^ Anacker, Christoph; Zunszain, Patricia A.; Carvalho, Livia A.; Pariante, Carmine M. (2011-04). "The glucocorticoid receptor: Pivot of depression and of antidepressant treatment?". Psychoneuroendocrinology. 36 (3): 415–425. doi:10.1016/j.psyneuen.2010.03.007. PMC 3513407. PMID 20399565. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  31. ^ Mazarati A, Lu X, Shinmei S, Badie-Mahdavi H, Bartfai T (2004). "Patterns of seizures, hippocampal injury and neurogenesis in three models of status epilepticus in galanin receptor type 1 (GalR1) knockout mice". Neuroscience. 128 (2): 431–41. doi:10.1016/j.neuroscience.2004.06.052. PMC 1360211. PMID 15350653.
  32. ^ Zhang L, Robertson CR, Green BR, Pruess TH, White HS, Bulaj G (Mar 2009). "Structural requirements for a lipoamino acid in modulating the anticonvulsant activities of systemically active galanin analogues". Journal of Medicinal Chemistry. 52 (5): 1310–6. doi:10.1021/jm801397w. PMC 2765488. PMID 19199479.
  33. ^ Bulaj G, Green BR, Lee HK, Robertson CR, White K, Zhang L, Sochanska M, Flynn SP, Scholl EA, Pruess TH, Smith MD, White HS (Dec 2008). "Design, synthesis, and characterization of high-affinity, systemically-active galanin analogues with potent anticonvulsant activities". Journal of Medicinal Chemistry. 51 (24): 8038–47. doi:10.1021/jm801088x. PMID 19053761.
  34. ^ White HS, Scholl EA, Klein BD, Flynn SP, Pruess TH, Green BR, Zhang L, Bulaj G (Apr 2009). "Developing novel antiepileptic drugs: characterization of NAX 5055, a systemically-active galanin analog, in epilepsy models". Neurotherapeutics. 6 (2): 372–80. doi:10.1016/j.nurt.2009.01.001. PMC 4402707. PMID 19332332.
  35. ^ a b Hobson, S-A.; Bacon, A.; Elliot-Hunt, C. R.; Holmes, F. E.; Kerr, N. C. H.; Pope, R.; Vanderplank, P.; Wynick, D. (2010), Hökfelt, Tomas (ed.), "Galanin Acts as a Trophic Factor to the Central and Peripheral Nervous Systems", Galanin, vol. 102, Springer Basel, pp. 25–38, doi:10.1007/978-3-0346-0228-0_3, ISBN 978-3-0346-0227-3, retrieved 2020-03-01
  36. ^ a b c Xu, Xiao-Jun; Hökfelt, Tomas; Wiesenfeld-Hallin, Zsuzsanna (2010), Hökfelt, Tomas (ed.), "Galanin and Spinal Pain Mechanisms: Past, Present, and Future", Galanin, vol. 102, Springer Basel, pp. 39–50, doi:10.1007/978-3-0346-0228-0_4, ISBN 978-3-0346-0227-3, retrieved 2020-03-01

Further reading

  • Vrontakis ME (Dec 2002). "Galanin: a biologically active peptide". Current Drug Targets. CNS and Neurological Disorders. 1 (6): 531–41. doi:10.2174/1568007023338914. PMID 12769595.
  • Mufson EJ, Counts SE, Perez SE, Binder L (Jun 2005). "Galanin plasticity in the cholinergic basal forebrain in Alzheimer's disease and transgenic mice". Neuropeptides. 39 (3): 233–7. doi:10.1016/j.npep.2004.12.005. PMID 15893372.
  • Robinson JK, Bartfai T, Langel U (Jun 2006). "Galanin/GALP receptors and CNS homeostatic processes". CNS & Neurological Disorders Drug Targets. 5 (3): 327–34. doi:10.2174/187152706777452281. PMID 16787232.
  • McKnight GL, Karlsen AE, Kowalyk S, Mathewes SL, Sheppard PO, O'Hara PJ, Taborsky GJ (Jan 1992). "Sequence of human galanin and its inhibition of glucose-stimulated insulin secretion from RIN cells". Diabetes. 41 (1): 82–7. doi:10.2337/diabetes.41.1.82. PMID 1370155.
  • Gai WP, Geffen LB, Blessing WW (Aug 1990). "Galanin immunoreactive neurons in the human hypothalamus: colocalization with vasopressin-containing neurons". The Journal of Comparative Neurology. 298 (3): 265–80. doi:10.1002/cne.902980302. PMID 1698834.
  • Burleigh DE, Furness JB (Jun 1990). "Distribution and actions of galanin and vasoactive intestinal peptide in the human colon". Neuropeptides. 16 (2): 77–82. doi:10.1016/0143-4179(90)90115-F. PMID 1701228.
  • Fried G, Meister B, Rådestad A (Oct 1990). "Peptide-containing nerves in the human pregnant uterine cervix: an immunohistochemical study exploring the effect of RU 486 (mifepristone)". Human Reproduction. 5 (7): 870–6. doi:10.1093/oxfordjournals.humrep.a137200. PMID 1702449.
  • Hyde JF, Engle MG, Maley BE (Jul 1991). "Colocalization of galanin and prolactin within secretory granules of anterior pituitary cells in estrogen-treated Fischer 344 rats". Endocrinology. 129 (1): 270–6. doi:10.1210/endo-129-1-270. PMID 1711463.
  • Bennet WM, Hill SF, Ghatei MA, Bloom SR (Sep 1991). "Galanin in the normal human pituitary and brain and in pituitary adenomas". The Journal of Endocrinology. 130 (3): 463–7. doi:10.1677/joe.0.1300463. PMID 1719117.
  • Schmidt WE, Kratzin H, Eckart K, Drevs D, Mundkowski G, Clemens A, Katsoulis S, Schäfer H, Gallwitz B, Creutzfeldt W (Dec 1991). "Isolation and primary structure of pituitary human galanin, a 30-residue nonamidated neuropeptide". Proceedings of the National Academy of Sciences of the United States of America. 88 (24): 11435–9. doi:10.1073/pnas.88.24.11435. PMC 53150. PMID 1722333.
  • Bauer FE, Christofides ND, Hacker GW, Blank MA, Polak JM, Bloom SR (1986). "Distribution of galanin immunoreactivity in the genitourinary tract of man and rat". Peptides. 7 (1): 5–10. doi:10.1016/0196-9781(86)90052-5. PMID 2423990.
  • Bauer FE, Adrian TE, Christofides ND, Ferri GL, Yanaihara N, Polak JM, Bloom SR (Oct 1986). "Distribution and molecular heterogeneity of galanin in human, pig, guinea pig, and rat gastrointestinal tracts". Gastroenterology. 91 (4): 877–83. doi:10.1016/0016-5085(86)90689-x. PMID 2427385.
  • Tainio H, Vaalasti A, Rechardt L (1987). "The distribution of substance P-, CGRP-, galanin- and ANP-like immunoreactive nerves in human sweat glands". The Histochemical Journal. 19 (6–7): 375–80. doi:10.1007/BF01680455. PMID 2444569.
  • Maggi CA, Santicioli P, Patacchini R, Turini D, Barbanti G, Beneforti P, Giuliani S, Meli A (Nov 1987). "Galanin: a potent modulator of excitatory neurotransmission in the human urinary bladder". European Journal of Pharmacology. 143 (1): 135–7. doi:10.1016/0014-2999(87)90744-8. PMID 2446889.
  • Marti E, Gibson SJ, Polak JM, Facer P, Springall DR, Van Aswegen G, Aitchison M, Koltzenburg M (Dec 1987). "Ontogeny of peptide- and amine-containing neurones in motor, sensory, and autonomic regions of rat and human spinal cord, dorsal root ganglia, and rat skin". The Journal of Comparative Neurology. 266 (3): 332–59. doi:10.1002/cne.902660304. PMID 2447134.
  • Beal MF, Clevens RA, Chattha GK, MacGarvey UM, Mazurek MF, Gabriel SM (Dec 1988). "Galanin-like immunoreactivity is unchanged in Alzheimer's disease and Parkinson's disease dementia cerebral cortex". Journal of Neurochemistry. 51 (6): 1935–41. doi:10.1111/j.1471-4159.1988.tb01181.x. PMID 2460590.
  • Berrettini WH, Kaye WH, Sunderland T, May C, Gwirtsman HE, Mellow A, Albright A (1989). "Galanin immunoreactivity in human CSF: studies in eating disorders and Alzheimer's disease". Neuropsychobiology. 19 (2): 64–8. doi:10.1159/000118436. PMID 2465504.

External links

Template:Neuropeptidergics

Retrieved from "https://en.wikipedia.org/w/index.php?title=Galanin&oldid=949019544"