Human Pluripotent Stem Cells-Based Therapies for Neurodegenerative Diseases: Current Status and Challenges.

Neurodegenerative diseases are characterized by irreversible cell damage, loss of neuronal cells and limited regeneration potential of the adult nervous system. Pluripotent stem cells are capable of differentiating into the multitude of cell types that compose the central and peripheral nervous systems and so have become the major focus of cell replacement therapies for the treatment of neurological disorders. Human embryonic stem cell (hESC) and human induced pluripotent stem cell (hiPSC)-derived cells have both been extensively studied as cell therapies in a wide range of neurodegenerative disease models in rodents and non-human primates, including Parkinson's disease, stroke, epilepsy, spinal cord injury, Alzheimer's disease, multiple sclerosis and pain.

The amyotrophic lateral sclerosis 8 protein, VAP, is required for ER protein quality control.

A familial form of Amyotrophic lateral sclerosis (ALS8) is caused by a point mutation (P56S) in the vesicle-associated membrane protein associated protein B (VapB). Human VapB and Drosophila Vap-33-1 (Vap) are homologous type II transmembrane proteins that are localized to the ER. However, the precise consequences of the defects associated with the P56S mutation in the endoplasmic reticulum (ER) and its role in the pathology of ALS are not well understood.