Galanin

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GAL

"'we dreamt deaf' [2015] by nicholas galanin" by?brain_____heart

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Identifiers

Aliases

GAL, GAL-GMAP, GALN, GLNN, GMAP, ETL8, galanin and GMAP prepropeptide

External IDs

OMIM:?137035?MGI:?95637?HomoloGene:?7724?GeneCards:?GAL

showGene location (Human)

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showGene location (Mouse)

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showRNA expression?pattern

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showGene ontology

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Orthologs

Species

Human

Mouse

?

Entrez

?

51083

?

?

14419

?

?

Ensembl

?

ENSG00000069482

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ENSMUSG00000024907

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?

UniProt

?

P22466

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?

P47212

?

?

RefSeq (mRNA)

?

NM_015973

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?

NM_010253
NM_001329667

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?

RefSeq (protein)

?

NP_057057

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NP_001316596
NP_034383

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?

Location (UCSC)

Chr 11: 68.68 – 68.69 Mb

Chr 19: 3.41 – 3.41 Mb

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PubMedsearch

[3]

[4]

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Wikidata

View/Edit Human

View/Edit Mouse

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?

Galanin

Identifiers

CAS Number

·?88813-36-9?

ChemSpider

·?none

ChEMBL

·?ChEMBL501079?

Chemical and physical data

Formula

C146H213N43O40

Molar mass

3210.571?g·mol?1

??(what is this?)??(verify)

Galanin?is a?neuropeptide?encoded by the?GAL?gene

（gene直接編碼galanin蛋白質(zhì)，這還是比較少見，基因一般都是編碼目標(biāo)蛋白質(zhì)的precursor。）

,[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]

Much of galanin's functional role is still undiscovered. Galanin is closely 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.

(Galanin抑制medial preoptic area,從而提升parental behAViour。)

[8]?Galanin is linked to a number of diseases including?Alzheimer's disease,?epilepsy?as well as?depression,?eating disorders,?cancer, and?addiction.[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]

Contents

·?1Discovery

·?2Tissue distribution

·?3Structure

·?4Receptors

·?5Clinical characteristics

·?5.1APPetite

·?5.2Addiction

·?5.3Alzheimer's disease

·?5.4Cognitive performance

·?5.5Depression

·?5.6Epilepsy

·?5.7In development

·?5.8Pain and neuroprotection

·?5.9Parental role in mice

·?6See also

·?7References

·?8External links

Discovery[edit]

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[edit]

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 it?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[edit]

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

Symbol

Galanin

Pfam

PF01296

InterPro

IPR008174

PROSITE

PDOC00673

showAVailable protein structures:

?

?

Galanin message associated peptide (GMAP)

Identifiers

Symbol

GMAP

Pfam

PF06540

InterPro

IPR013068

showAVailable protein structures:

?

?

Receptors[edit]

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[edit]

APPetite[edit]

Injections of galanin into the?lateral ventricle?or directly into 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.[23]?Galanin is an inhibitor of pancreatic secretion of insulin.[19]

Addiction[edit]

Galanin plays a role in addiction regulation.[24]?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.[24]

Alzheimer's disease[edit]

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.[25]?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.[25][26]

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][25]

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.[27]

Cognitive performance[edit]

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

Depression[edit]

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.[15]?Stimulation of the Gal1 and Gal3 receptors result in depression-like behAViors, whereas stimulation of the Gal2 receptor results in reduced depression-like behAViors.[15]?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.[15]?Increased levels of glucocorticoid hormones is common in those who suffer from depression.[28]

Epilepsy[edit]

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.[29][30]?An agonist antiepileptic drug candidate is NAX 5055.[31][32]

In development[edit]

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[edit]

Galanin plays an inhibitory role in pain processing,[33]?with high doses hAVing been shown to reduce pain.[19]?When galanin is added to the spinal cord,?neuropathic pain?is reduced.[34]?Along with this, galanin is believed to be effective in reducing spinal hyperexcitability.[34]?Sensory neurons increasingly release galanin when they are damaged.[34]?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.[33]

Parental role in mice[edit]

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]

galanin在神經(jīng)細(xì)胞受損時(shí)大量出現(xiàn)，從而修復(fù)之。這不禁讓我想到了許多神經(jīng)遞質(zhì)是自由基的本質(zhì)，過(guò)多的自由基會(huì)損傷細(xì)胞膜，雖然有褪黑素可以與自由基結(jié)合，但是galanin能夠精準(zhǔn)出現(xiàn)在受損神經(jīng)細(xì)胞的位置，同時(shí)還起到抑制這里神經(jīng)細(xì)胞的作用。記得prostaglandin是在細(xì)胞的細(xì)胞膜破碎的時(shí)候被釋放，從而增加了痛覺(jué)神經(jīng)細(xì)胞的敏感性，而阿司匹林類藥能夠抑制prostaglandin的這個(gè)效果，從而減少疼痛的輸入，從某種角度也是減少了對(duì)pre-optic area的輸入，從而也不用費(fèi)力讓magnus?raphe nucleus向spinal cord投放serotonin，也可以不用讓nucleus raphe pallidus釋放serotonin。