TY - JOUR
T1 - Research Progress of α-Synuclein Aggregation Inhibitors for Potential Parkinson’s Disease Treatment
AU - Kalsoom, Iqra
AU - Wang, Yuanhao
AU - Li, Bo
AU - Wen, Hongliang
N1 - Publisher Copyright:
© 2023 Bentham Science Publishers.
PY - 2023
Y1 - 2023
N2 - Introduction: Parkinson’s disease (PD) is characterized by fibrillation of disordered proteins known as Lewy bodies in the substantia nigra that also undergo progressive neurodegeneration. The aggregation of α-synuclein (α-syn) is a hallmark and potentially a critical step in the development of Parkinson’s disease and other synucleinopathies. The synaptic vesicle protein α-syn is a small, abundant, highly conserved disordered protein and the causative agent of neurodegenerative diseases. Several novel pharmacologically active compounds are used to treat PD and other neurodegenerative disorders. Though, the mechanism through which these molecules inhibit the α-syn aggregation is still not fully understood. Objective: This review article is focused on the recent advancements in compounds that can inhibit the development of α-syn fibrillation and oligomerization. Methods: The current review article is based on the most recent and frequently cited papers from Google Scholar, SciFinder, and Researchgate sources. Description: In the progression of PD, the mechanism of α-syn aggregation involves the structural transformation from monomers into amyloid fibrils. As the accumulation of α-syn in the brain has been linked to many disorders, the recent search for disease-modifying medications mainly focused on modifying the α-syn aggregation. This review contains a detailed report of literature findings and il-lustrates the unique structural features, structure-activity relationship, and therapeutic potential of the natural flavonoids in the inhibition of α-syn are also discussed. Conclusion: Recently, many naturally occurring molecules such as curcumin, polyphenols, nicotine, EGCG, and stilbene have been recognized to inhibit the fibrillation and toxicity of α-syn. Therefore, knowing the α-synuclein filament's structure and how they originate will help invent particular bi-omarkers for synucleinopathies and develop reliable and effective mechanism-based therapeutics. We hope the information this review provides may help evaluate novel chemical compounds, such as α-syn aggregation inhibitors, and will contribute to developing novel drugs for treating Parkinson’s dis-ease.
AB - Introduction: Parkinson’s disease (PD) is characterized by fibrillation of disordered proteins known as Lewy bodies in the substantia nigra that also undergo progressive neurodegeneration. The aggregation of α-synuclein (α-syn) is a hallmark and potentially a critical step in the development of Parkinson’s disease and other synucleinopathies. The synaptic vesicle protein α-syn is a small, abundant, highly conserved disordered protein and the causative agent of neurodegenerative diseases. Several novel pharmacologically active compounds are used to treat PD and other neurodegenerative disorders. Though, the mechanism through which these molecules inhibit the α-syn aggregation is still not fully understood. Objective: This review article is focused on the recent advancements in compounds that can inhibit the development of α-syn fibrillation and oligomerization. Methods: The current review article is based on the most recent and frequently cited papers from Google Scholar, SciFinder, and Researchgate sources. Description: In the progression of PD, the mechanism of α-syn aggregation involves the structural transformation from monomers into amyloid fibrils. As the accumulation of α-syn in the brain has been linked to many disorders, the recent search for disease-modifying medications mainly focused on modifying the α-syn aggregation. This review contains a detailed report of literature findings and il-lustrates the unique structural features, structure-activity relationship, and therapeutic potential of the natural flavonoids in the inhibition of α-syn are also discussed. Conclusion: Recently, many naturally occurring molecules such as curcumin, polyphenols, nicotine, EGCG, and stilbene have been recognized to inhibit the fibrillation and toxicity of α-syn. Therefore, knowing the α-synuclein filament's structure and how they originate will help invent particular bi-omarkers for synucleinopathies and develop reliable and effective mechanism-based therapeutics. We hope the information this review provides may help evaluate novel chemical compounds, such as α-syn aggregation inhibitors, and will contribute to developing novel drugs for treating Parkinson’s dis-ease.
KW - Inhibitors
KW - Intrinsically disordered protein
KW - Parkinson’s disease
KW - Presynaptic
KW - Structure-activity relationship
KW - α-Synuclein aggregation
UR - http://www.scopus.com/inward/record.url?scp=85172910706&partnerID=8YFLogxK
U2 - 10.2174/1389557523666230517163501
DO - 10.2174/1389557523666230517163501
M3 - Short survey
C2 - 37198991
AN - SCOPUS:85172910706
SN - 1389-5575
VL - 23
SP - 1959
EP - 1974
JO - Mini-Reviews in Medicinal Chemistry
JF - Mini-Reviews in Medicinal Chemistry
IS - 20
ER -