Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia

We have previously reported a large Danish pedigree with autosomal dominant frontotemporal dementia (FTD) linked to chromosome 3 (FTD3). Here we identify a mutation in CHMP2B, encoding a component of the endosomal ESCRTIII complex, and show that it results in aberrant mRNA splicing in tissue samples from affected members of this family. We also describe an additional missense mutation in an unrelated individual with FTD. Aberration in the endosomal ESCRTIII complex may result in FTD and neurodegenerative disease.     

Physiological and pathological properties of α-synuclein

alpha-Synuclein belongs to a small group of natively unfolded proteins that can transiently bind to lipid membranes and acquire a partial alpha-helical conformation. Under certain pathogenic conditions, alpha-synuclein aggregates to form oligomers and insoluble fibrils with increased ss-sheet configuration. Although genetic mutations and multiplications of the gene have been found in familial cases, the mechanism by which this protein aggregates in sporadic cases of Parkinson's disease, dementia with Lewy bodies and multisystem atrophy is not fully understood. Here we review the function of alpha-synuclein and recent insight into the mechanisms by which it aggregates.