Synuclein proteins

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Synuclein proteins

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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Synucleins are small soluble proteins that share structural motifs. They are primarily expressed in neuronal cells. The human genome has three synuclein genes, that encode synucleins alpha, beta and gamma. They are proposed to be involved in the regulation of membrane stability and/or turnover in healthy cells. Most is known about synuclein alpha due to its role in Parkinson's disease and other neurodegenerative diseases.

Targets

3285

synuclein alpha Show summary »« Hide summary

Target Id

3285

Nomenclature

synuclein alpha

Previous and unofficial names

α-syn | alpha-synuclein | α-synuclein | PARK4 | Parkinson disease (autosomal dominant, Lewy body) 4

Genes

SNCA (Hs), Snca (Mm), Snca (Rn)

Ensembl ID

ENSG00000145335 (Hs), ENSMUSG00000025889 (Mm), ENSRNOG00000008656 (Rn)

UniProtKB AC

P37840 (Hs), O55042 (Mm), P37377 (Rn)

Antibodies

prasinezumab (Binding) pK_d 10.3 [3], 7.7 [3]

cinpanemab (Binding) pK_d 7.0 [10]

Comment

The formation of abnormal and toxic synuclein alpha oligomers and larger fibrilar aggregates underlies neurodegeneration in Parkinson's disease and other neurodegenerative diseases. There has therefore been much interest in developing therapeutics that are able to prevent formation or functionally block these aggregates as potential disease-modifying options to slow disease progression. As of early 2024, clinical evidence was beginning to demonstrate two pharmaceutical mechanisms that offered disease-modifying efficacy (in patients in the early stages of Parkinson's disease): anti-diabetes GLP-1 agonist drugs (lixisenatide and exenatide/exendin-4 for example) [1-2,7] and the monoclonal antibody prasinezumab that selectively targets aggregated forms synuclein alpha [8]. It remains to be determined if these mechanisms hold in larger clinical studies.

synuclein beta Show summary »« Hide summary

Target Id	3286
Nomenclature	synuclein beta
Previous and unofficial names	β-syn \| β-synuclein
Genes	SNCB (Hs), Sncb (Mm), Sncb (Rn)
Ensembl ID	ENSG00000074317 (Hs), ENSMUSG00000034891 (Mm), ENSRNOG00000018039 (Rn)
UniProtKB AC	Q16143 (Hs), Q91ZZ3 (Mm), Q63754 (Rn)
Comment	Synuclein beta has been found as a non-amyloid component in Alzheimer's disease plaques, but is not detected in the Lewy bodies associated with Parkinson's disease.

synuclein gamma Show summary »« Hide summary

Target Id	3287
Nomenclature	synuclein gamma
Previous and unofficial names	breast cancer-specific gene 1 (BCSG1) \| γ-synuclein \| synoretin \| synuclein γ
Genes	SNCG (Hs), Sncg (Mm), Sncg (Rn)
Ensembl ID	ENSG00000173267 (Hs), ENSMUSG00000023064 (Mm), ENSRNOG00000058006 (Rn)
UniProtKB AC	O76070 (Hs), Q9Z0F7 (Mm)
Comment	Potential roles in modulating axonal architecture and neurofilament network integrity. Experimantal evidence suggests synuclein gamma as a potential biomarker for some cancers [4-6,9,11].

References

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1. Athauda D, Maclagan K, Skene SS, Bajwa-Joseph M, Letchford D, Chowdhury K, Hibbert S, Budnik N, Zampedri L, Dickson J et al.. (2017) Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial. Lancet, 390 (10103): 1664-1675. [PMID:28781108]

2. Aviles-Olmos I, Dickson J, Kefalopoulou Z, Djamshidian A, Ell P, Soderlund T, Whitton P, Wyse R, Isaacs T, Lees A et al.. (2013) Exenatide and the treatment of patients with Parkinson's disease. J Clin Invest, 123 (6): 2730-6. [PMID:23728174]

3. Jankovic J, Goodman I, Safirstein B, Marmon TK, Schenk DB, Koller M, Zago W, Ness DK, Griffith SG, Grundman M et al.. (2018) Safety and Tolerability of Multiple Ascending Doses of PRX002/RG7935, an Anti-α-Synuclein Monoclonal Antibody, in Patients With Parkinson Disease: A Randomized Clinical Trial. JAMA Neurol, 75 (10): 1206-1214. [PMID:29913017]

4. Li J, Li P, Li J, Yang H, Liu G, Shen P, Jiang G. (2022) Effects of the Methylation Levels for the Breast Cancer Associated Genes BCSG1 and BRCA1 on Cellular Proliferation and Migration. Genet Test Mol Biomarkers, 26 (9): 422-429. [PMID:36166741]

5. Li Y, Pan Q, Cheng M, Wu Z. (2023) Identification and validation of anoikis-associated gene SNCG as a prognostic biomarker in gastric cancer. Aging (Albany NY), 15 (7): 2541-2553. [PMID:36996495]

6. Liu J, Shao T, Zhang J, Liu Q, Hua H, Zhang H, Wang J, Luo T, Shi YE, Jiang Y. (2022) Gamma synuclein promotes cancer metastasis through the MKK3/6-p38MAPK cascade. Int J Biol Sci, 18 (8): 3167-3177. [PMID:35637967]

7. Meissner WG, Remy P, Giordana C, Maltête D, Derkinderen P, Houéto JL, Anheim M, Benatru I, Boraud T, Brefel-Courbon C et al.. (2024) Trial of Lixisenatide in Early Parkinson's Disease. N Engl J Med, 390 (13): 1176-1185. [PMID:38598572]

8. Pagano G, Taylor KI, Anzures Cabrera J, Simuni T, Marek K, Postuma RB, Pavese N, Stocchi F, Brockmann K, Svoboda H et al.. (2024) Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson's disease. Nat Med, [Epub ahead of print]. [PMID:38622249]

9. Pan Y, Zheng Y, Yang J, Wei Y, Wu H, Liu S, Yin A, Hu J, Zeng Y. (2022) A new biomarker for the early diagnosis of gastric cancer: gastric juice- and serum-derived SNCG. Future Oncol, 18 (28): 3179-3190. [PMID:35947016]

10. Weihofen A, Liu Y, Arndt JW, Huy C, Quan C, Smith BA, Baeriswyl JL, Cavegn N, Senn L, Su L et al.. (2019) Development of an aggregate-selective, human-derived α-synuclein antibody BIIB054 that ameliorates disease phenotypes in Parkinson's disease models. Neurobiol Dis, 124: 276-288. [PMID:30381260]

11. Yang J, Pan Y, Peng L, Zhang L, Zhao J, Zheng Z, Zheng J, Xu X, Zeng Y. (2022) Upregulation of Synuclein-γ and Snai1 Contributes to Poor Clinical Prognosis in Oral Squamous Cell Carcinoma Patients. Biomed Res Int, 2022: 6534626. [PMID:35434126]

How to cite this family page

Database page citation:

Synuclein proteins. Accessed on 19/09/2024. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1100.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Buneman OP, Faccenda E, Harding SD, Spedding M, Cidlowski JA, Fabbro D, Davenport AP, Striessnig J, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Introduction and Other Protein Targets. Br J Pharmacol. 180 Suppl 2:S1-22.