With the aging of society, neurological disorders such as Parkinson’s diseases (PD) and Multiple System Atrophy (MSA) cause serious socio-economic problem for the society. Currently no appropriate therapy for the healing of the synucleinopathy. Alpha-Synuclein (SYN), a hallmark and these diseases and Tubulin Polymerization Promoting Protein (TPPP/p25), discovered and denoted by our research group, are expressed in neurons and oligodendrocytes in normal brain, respectively; however, they are co-enriched and co-localized in both cell types leading to development of in the case of PD and MSA. These neomorphic moonlighting proteins displaying both physiological and pathological functions with chameleon characteristics, thus neither of them is ideal target for pharmaceutical intervention. Due to the recognition that the soluble homo- and hetero-oligomers of SYN and TPPP/p25 are fatal species in the development of parkinsonism, we evolved a new innovative strategy for the identification of specific drug target. The interfaces of the pathological SYN-TPPP/p25 complex were identified and validated, the targeting of which prevents/destructs of pathological complex without affecting physiological functions of the partner proteins. The innovative strategy established could lead to the development of specific peptidomimetic foldamer-like drugs for the therapy of synucleinopathies.
Citation: Online Meeting on Parkinson’s Disease (OMPD-2020). J Neurol Exp Neurosci 6(2): S1-S3.