Antibodies against alpha‐synuclein: tools and therapies. Issue 5 (25th June 2019) - Vaikath, Nishant N.
Abstract: Synucleinopathies including Parkinson's disease, dementia with Lewy bodies and multiple system atrophy are characterized by the abnormal accumulation and propagation of α‐synuclein (α‐syn) pathology in the central and peripheral nervous system as Lewy bodies or glial cytoplasmic inclusions. Several antibodies against α‐syn have been developed since it was first detected as the major component of Lewy bodies and glial cytoplasmic inclusions. Over the years, researchers have generated specific antibodies that alleviate the accumulation of intracellular aggregated α‐syn and associated pathology in cellular and preclinical models of synucleinopathies. So far, antibodies have been the first choice as tools for research and diagnosis and currently, a wide variety of antibody fragments have been developed as an alternative to full‐length antibodies for increasing its therapeutic usefulness. Recently, conformation specific antibody‐based approaches have been found to be promising as therapeutic strategies, both to block α‐syn aggregation and ameliorate the resultant cytotoxicity, and as diagnostic tools. In this review, we summarize different α‐syn specific antibodies and provide their usefulness in tackling synucleinopathies. This article is part of the Special Issue "Synuclein". Abstract : α‐Synuclein (α‐syn) under physiological and pathological conditions: Under physiological conditions, α‐syn is an unstructured soluble monomer bound to membranes with two α‐helices. Under pathological conditions, α‐syn dimerizes and subsequently aggregates into oligomers/protofibrils, which ultimately form into mature fibrils. Until now it still remains unclear as to which strain of α‐syn is most toxic. We suggest that there is a pressing need for further characterization of the diversity and clinico‐pathological relevance of distinct strains of α‐syn in Lewy body disease. Hence antibody‐based approaches, targeting different strains of α‐syn, could accelerate the understanding of the complexities in synucleinopathies. This article is part of the Special Issue "Synuclein".