000282332 001__ 282332 000282332 005__ 20251120154925.0 000282332 0247_ $$2doi$$a10.1007/s12035-025-05359-6 000282332 0247_ $$2pmid$$apmid:41258277 000282332 0247_ $$2ISSN$$a0893-7648 000282332 0247_ $$2ISSN$$a1559-1182 000282332 037__ $$aDZNE-2025-01293 000282332 041__ $$aEnglish 000282332 082__ $$a570 000282332 1001_ $$aZahra, Fatima Tu$$b0 000282332 245__ $$aSynuclein Proteoforms: Role in Health and Disease. 000282332 260__ $$aTotowa, NJ$$bHumana Press$$c2025 000282332 3367_ $$2DRIVER$$aarticle 000282332 3367_ $$2DataCite$$aOutput Types/Journal article 000282332 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1763650020_2192$$xReview Article 000282332 3367_ $$2BibTeX$$aARTICLE 000282332 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000282332 3367_ $$00$$2EndNote$$aJournal Article 000282332 520__ $$aSynucleins α, β, and γ are inherently disordered proteins that play essential roles in neuronal physiology and are increasingly recognized as key players in neurodegenerative disease mechanisms. The molecular basis of synucleinopathies, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, is the pathological aggregation and misfolding of synucleins. However, the biological significance of the diverse synuclein proteoforms that result from alternative splicing, extensive post-translational modifications, and conformational heterogeneity is still not fully understood. This review systematically incorporates current knowledge of the structural and functional diversity of synuclein proteoforms, highlighting their molecular interactions and aggregation pathways. We investigate the regulatory effects of β and γ-synucleins (β-syn and γ-syn), which have different physiological functions and clinical applications in addition to influencing α-synuclein (α-syn) aggregation. In addition to synucleins' involvement in the central nervous system, recent findings show their role in immune regulation and functions in peripheral tissues, highlighting their systemic relevance. Controversial aspects, such as the mechanisms of prion-like propagation, proteoform-specific toxicity, and differential cellular vulnerability, are thoroughly analyzed. Synuclein proteoforms have been thoroughly characterized due to developments in molecular imaging and proteomic techniques, opening the door for targeted treatment approaches. Developing novel treatments for mitigating the progression of synucleinopathies and enhancing patient outcomes requires an understanding of the complex biology of synuclein proteoforms. The goal of this study is to present a thorough framework that connects translational research and molecular neurobiology in disorders related to synuclein. 000282332 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x0 000282332 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000282332 650_7 $$2Other$$aPTMs 000282332 650_7 $$2Other$$aProtein misfolding 000282332 650_7 $$2Other$$aProteoforms 000282332 650_7 $$2Other$$aSynuclein 000282332 650_7 $$2Other$$aSynucleinopathies 000282332 650_7 $$2NLM Chemicals$$aSynucleins 000282332 650_7 $$2NLM Chemicals$$aalpha-Synuclein 000282332 650_7 $$2NLM Chemicals$$aProtein Isoforms 000282332 650_2 $$2MeSH$$aHumans 000282332 650_2 $$2MeSH$$aAnimals 000282332 650_2 $$2MeSH$$aSynucleins: metabolism 000282332 650_2 $$2MeSH$$aSynucleins: chemistry 000282332 650_2 $$2MeSH$$aHealth 000282332 650_2 $$2MeSH$$aSynucleinopathies: metabolism 000282332 650_2 $$2MeSH$$aalpha-Synuclein: metabolism 000282332 650_2 $$2MeSH$$aNeurodegenerative Diseases: metabolism 000282332 650_2 $$2MeSH$$aProtein Isoforms: metabolism 000282332 7001_ $$aKayani, Hooreen$$b1 000282332 7001_ $$aNoreen, Samra$$b2 000282332 7001_ $$0P:(DE-2719)9001208$$aNoor, Aneeqa$$b3 000282332 7001_ $$0P:(DE-2719)9000358$$aZafar, Saima$$b4$$eLast author$$udzne 000282332 773__ $$0PERI:(DE-600)2079384-4$$a10.1007/s12035-025-05359-6$$gVol. 63, no. 1, p. 87$$n1$$p87$$tMolecular neurobiology$$v63$$x0893-7648$$y2025 000282332 8564_ $$uhttps://pub.dzne.de/record/282332/files/DZNE-2025-01291_Restricted.pdf 000282332 8564_ $$uhttps://pub.dzne.de/record/282332/files/DZNE-2025-01291_Restricted.pdf?subformat=pdfa$$xpdfa 000282332 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9000358$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b4$$kDZNE 000282332 9131_ $$0G:(DE-HGF)POF4-353$$1G:(DE-HGF)POF4-350$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lNeurodegenerative Diseases$$vClinical and Health Care Research$$x0 000282332 915__ $$0StatID:(DE-HGF)3002$$2StatID$$aDEAL Springer$$d2025-01-07$$wger 000282332 915__ $$0StatID:(DE-HGF)3002$$2StatID$$aDEAL Springer$$d2025-01-07$$wger 000282332 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2025-01-07 000282332 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2025-01-07 000282332 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2025-01-07 000282332 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2025-01-07 000282332 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2025-01-07 000282332 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2025-01-07 000282332 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2025-01-07 000282332 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2025-01-07 000282332 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bMOL NEUROBIOL : 2022$$d2025-01-07 000282332 915__ $$0StatID:(DE-HGF)9905$$2StatID$$aIF >= 5$$bMOL NEUROBIOL : 2022$$d2025-01-07 000282332 9201_ $$0I:(DE-2719)1440011-1$$kAG Zerr$$lTranslational Studies and Biomarker$$x0 000282332 980__ $$ajournal 000282332 980__ $$aEDITORS 000282332 980__ $$aVDBINPRINT 000282332 980__ $$aI:(DE-2719)1440011-1 000282332 980__ $$aUNRESTRICTED