alpha-synuclein

Class

active immunotherapy (vaccine)

Alpha-synuclein is a small protein concentrated at presynaptic nerve terminals, where it is thought to help regulate the release and recycling of synaptic vesicles, the structures that store and release neurotransmitters. Under normal conditions it exists largely as an unstructured, soluble monomer. In several neurodegenerative disorders, collectively called synucleinopathies, the protein misfolds and aggregates into oligomers and insoluble fibrils that accumulate as Lewy bodies inside neurons. These aggregates are toxic to cells and appear to spread from neuron to neuron in a manner reminiscent of prion proteins, correlating with disease progression across brain regions. Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy all feature this pathological process, making alpha-synuclein a central therapeutic target for slowing or halting neurodegeneration rather than merely treating symptoms. Because the toxic, aggregated forms of the protein differ structurally from the normal monomer, therapeutic strategies aim to reduce the burden of pathological alpha-synuclein while sparing its normal function. Approaches include active immunization, which trains the immune system to generate antibodies against the protein; passive administration of pre-made antibodies designed to recognize aggregated or extracellular forms; and antisense oligonucleotides that reduce production of the protein at its source. Each strategy intervenes at a different point along the same underlying disease pathway.