HYBRID EVENT: You can participate in person at Boston, Massachusetts, USA or Virtually from your home or work.

8th Edition of International Conference on Neurology and Brain Disorders

October 19-21, 2023

October 19 -21, 2023 | Boston, Massachusetts, USA
INBC 2023

Manish kumar

Speaker at Neurology and Brain Disorders 2023 - Manish kumar
Title : Length-dependent RNA foci formation and repeat associated non-AUG dependent translation in SCA12 patient derived neural stem cells: hallmarks to pathogenesis


Spinocerebellar ataxia type-12 (SCA12) is a neurodegenerative disease and one of the most prominent SCA-subtype in India that exhibits a unique progressive tremor/ataxia syndrome induced by triplet (CAG) repeat expansion in 5’ UTR region of PPP2R2B. So far, no study has been done to investigate the pathological hallmarks using the appropriate disease model. Therefore, we aimed to establish human iPSC derived SCA12 neuronal cell lines to study the cellular pathological mechanisms induced by CAG expansion. As reported previously, we found that the expression of PPP2R2B gene increases with CAG expansion. Further, expanded CAG in PPP2R2B transcript causes formation of RNA Foci inside the nucleus of the patient-derived neural stem cells, which in turn may sequester many nuclear proteins, and inhibit their necessary functions. The ectopic expression of this expanded CAG transcript from PPP2R2B accelerates non-canonical Repeat Associated Non- Aug (RAN) translation in multiple frames and may produce aggregation-prone proteins in HEK cells, further validated in patient-derived neural stem cells using novel antibodies. Next, RNA-pull down assay in HEK cells and comparative whole RNA sequencing analysis of patient and control-derived neural stem cells followed by mass-spectrometric-based protein detection identified crucial proteins involved in protein homeostasis, vesicular trafficking, ion channels, mitochondrial fission, etc. shedding light on the mechanistic relationship between RAN translation and RNA foci, and their relative contributions to cellular dysfunction. Altogether, this study identifies the molecular signatures of SCA12 disorder using patient-derived neuronal cell lines, wherein RNA foci and RAN protein accumulation impact the functioning of crucial intracellular pathways. Furthermore, overlapping of these pathways in the same cell lines demonstrates the critical partaking of two modifiers in disease progression emphasizing the new therapeutic strategies that target both processes in repeat expansion disorders.


Manish studied Zoology (H) from Delhi University, India. After which he joined Dr. Mohammed Faruq, principal senior scientist in CSIR-IGIB, India, in 2017 and helped in development of diagnostics for rare genetic disorders. After developing his interest in Repeat expansion disorders he pursue his Ph.D. in “Deciphering the Pathogenesis of SCA-12 patients using iPSCs derived neurons” in the same lab. Also, he was involved in screening of COVID-19 samples, and generating iPSC for other rare genetic disorders. Till now, he has been authored in 5 research articles in reputed journals in his short career span.