A Unique Perspective on Lead Compounds for Dementia with the Lewy Body

Med Chem. 2023 Jul 18. doi: 10.2174/1573406419666230718121644. Online ahead of print.

Abstract

Dementia with Lewy Bodies is a neurodegenerative disorder characterised by abnormal α-Synuclein aggregate accumulation in Lewy Bodies and Lewy Neurites and the most common form of dementia after Alzheimer's disease. The presynaptic protein alpha-synuclein (α-Syn) regulates synaptic vesicle trafficking and the subsequent release of neurotransmitters in the brain. These aggregates go through a number of crucial stages, such as aggregation, oligomerization, and fibrillation. Treatment of this disorder is generally symptomatic. This necessitates the development of cutting-edge therapeutic approaches that can either stop or change the course of the diseases. Many studies have shown that α-synuclein is a significant therapeutic target and that inhibiting α-synuclein aggregation, oligomerization, and fibrillation is an important disease-modifying strategy. Since α-syn is a defining feature of Parkinson's disease, the current review provides an overview of plant phytochemicals and synthetic heterocyclic compounds that target α-syn in Parkinson's disease in order to develop new drugs for Dementia with Lewy Bodies.

Keywords: Dementia with Lewy body; Parkinson's disease; Presynaptic protein; αalpha;-Synuclein; αalpha;-Synuclein aggregation inhibitors..