alpha-synuclein oligomers

Class

oligomer modulator

Alpha-synuclein is a small protein normally involved in the trafficking of synaptic vesicles, the tiny sacs that store neurotransmitters at nerve endings. In several neurodegenerative diseases, collectively called synucleinopathies (including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy), this protein misfolds and clumps together. Rather than the large, insoluble fibrils that eventually form visible deposits called Lewy bodies, much of the damage is thought to arise from smaller, soluble clusters called oligomers, which form as an intermediate step in this aggregation process. These oligomers can disrupt neuronal membranes, impair mitochondrial and lysosomal function, and spread from cell to cell in a manner reminiscent of prion diseases, propagating dysfunction through neural circuits. Modulating alpha-synuclein oligomers means using an agent that interferes with this particular aggregation stage, ideally stabilizing harmless forms of the protein or preventing toxic oligomers from forming or spreading, without eliminating the protein's normal function. This approach is being explored broadly across synucleinopathies, where disease progression is linked to the accumulation and transmission of these misfolded species through the brain.