We are delighted to welcome Prof. Rupak Datta from Dept. of Biological Sciences, IISER Kolkata for an insightful talk on “Understanding the mechanism of neurodegeneration in MPS VII: Lessons from a fly model” on 31 August 2024, 11 AM at JIVAN – Centre for Research in Biological Sciences, Ramakrishna Mission Seva Pratisthan.

Speaker: Prof. Rupak Datta from Dept. of Biological Sciences, IISER Kolkata

Abstract

Mucopolysaccharidosis VII (MPSVII) is an autosomal recessive lysosomal storage disorder caused by Beta-glucuronidase (Beta-GUS) enzyme deficiency. MPS VII patients suffer from multiple organ dysfunctions leading to premature death in most cases. Progressive neurodegeneration and cognitive impairment are key symptoms of VII. However, the underlying mechanisms of neurodegeneration in MPS VII remains poorly understood. This presents a serious challenge in developing small molecule-based therapies to alleviate neurological problems faced by patients. We attempted to bridge this knowledge gap by employing a Drosophila model of MPS VII that we recently developed. This fly model of MPS VII mimicked many cardinal features of the disease including prominent signs of neuromuscular defects and loss of dopaminergic neurons. In this talk, I will discuss some of our recent findings that have significantly advanced the understanding of the neuropathogenesis of MPS VII by uncovering a mechanistic link between mitophagy defect, mitochondrial malfunction leading to brain energy deficits, and apoptotic neurodegeneration. Our results have led to the identification of critical molecular alterations in the autophagy-lysosomal pathway in the MPS VII fly brains, which may provide novel therapeutic leads for pharmacological interventions. I will also present some of our initial findings towards this goal.