Summary of - Delineating the Neuropathology of Lysosomal Storage Diseases Using Patient-Derived Induced Pluripotent Stem Cells

Document Type

Article

Abstract

Lysosomal storage diseases (LSDs) are caused by deficiency of lysosomal enzymes, required for developing brain and other organs. Neurological deficits are observed in 2/3rd of these patients that causes a high challenge to the medical field. This review highlights the information assembled from LSD patient-derived induced pluripotent stem cells (iPSCs) and derived cells on neuropathological defects with the disorder. This review identified pathologies such as defective neural stem cell migration and differentiation, substrate accumulation, axonal growth and defective myelination, defective calcium homeostasis, and changed electrophysiological properties in the patient-derived iPSCs. Further, defective lysosomes, endoplasmic reticulum, mitochondria, Golgi complex, autophagy, vesicle trafficking and signaling pathways were observed along with enhanced oxidative stress, neuroinflammation, defective blood-brain barrier function, gliosis, neurodegeneration, and altered transcriptomes in LSDs. The review further discussed drug discovery, synergistic effects of drugs, repurposing of drugs, targeted molecular therapies, gene therapy, and cell therapy for different LSDs.

Publication Date

2022

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