Galanin
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| Location (UCSC) | Chr 11: 68.68 – 68.69 Mb | Chr 19: 3.46 – 3.46 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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| Formula | C146H213N43O40 |
| Molar mass | 3210.571 g·mol−1 |
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Galanin is a
Much of galanin's functional role is still undiscovered. Galanin is closely involved in the modulation and inhibition of
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
Tissue distribution
Galanin is located predominantly in the central nervous system and
Structure
| Species | 1 | 6 | 11 | 16 | 21 | 26 ! |
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| 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
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]
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Receptors
Galanin signalling occurs through three classes of receptors,
Clinical characteristics
Appetite
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
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
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
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.[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]
Endocrine
Galanin inhibits the secretion of
Epilepsy
Galanin in the
In development
It has been shown that galanin plays a role in the control of the early post-natal
Pain and neuroprotection
Galanin plays an inhibitory role in pain processing,[34] with high doses having been shown to reduce pain.[19] When galanin is added to the spinal cord, neuropathic pain is reduced.[35] Along with this, galanin is believed to be effective in reducing spinal hyperexcitability.[35] Sensory neurons increasingly release galanin when they are damaged.[35] 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.[34]
Parental role in mice
Galanin-expressing neurons in the medial preoptic area of the brain are responsible for regulating aggression towards pups by male mice.[8]
Galanin-expressing neurons in the medial preoptic area are remodelled during pregnancy. Estrogen and progesterone genomic receptors in galanin (Gal)-expressing neurons control discrete aspected of plasticity.[36]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000069482 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024907 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ PMID 7508413.
- ^ S2CID 263470319.
- S2CID 8754964.
- ^ PMID 24828191.
- S2CID 19729607.
- S2CID 1108702.
- S2CID 207245197.
- ^ 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.
- ^ PMID 11712539.
- ^ S2CID 19878753.
- ^ PMID 21299068.
- S2CID 32774212.
- PMID 2448788.
- ^ PMID 21299061.
- ^ PMID 21299058.
- PMID 29462183.
- S2CID 19148582.
- ^ PMID 17604107.
- PMID 31705911.
- ^ S2CID 49486365.
- ^ PMID 18500641.
- PMID 14993421.
- S2CID 53192040.
- PMID 20399565.
- PMID 12818074. Retrieved 28 January 2023.
- PMID 15350653.
- PMID 19199479.
- PMID 19053761.
- PMID 19332332.
- ^ PMID 21299059.
- ^ PMID 21299060.
- PMID 37797007.
External links
- Galanin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)