Molecular Genetics of Frontotemporal Dementia Elucidated by Models-Defects in Endosomal⁻Lysosomal Pathway.

Frontotemporal dementia (FTD) is the second most common senile neurodegenerative disease. FTD is a heterogeneous disease that can be classified into several subtypes. A mutation in locus (), which encodes a component of endosomal sorting complex required for transport-III (ESCRT-III), is associated with a rare hereditary subtype of FTD linked to chromosome 3 (FTD-3). ESCRT is involved in critical cellular processes such as multivesicular body (MVB) formation during endosomal⁻lysosomal pathway and autophagy. ESCRT mutants causes diverse physiological defects primarily due to accumulation of endosomes and defective MVBs resulting in misregulation of signaling pathways. Charged multivesicular body protein 2B (CHMP2B) is important for neuronal physiology which especially rely on precise regulation of protein homeostasis due to their post-mitotic status. has proven to be an excellent model for charaterization of mechanistic underpinning of neurodegenerative disorders including FTD. In this review, current understanding of various FTD-related mutations is discussed with a focus on models of CHMP2B-associated FTD.