Recent studies also revealed that the Drp1 can interact with Aβ, phosphorylated τ, and mutant Htt affecting the mitochondrial shape, size, distribution, axonal transportation, and energy production in the AD and HD neuronal cells.
In the central nervous system (CNS), EVs have been suggested as potential carriers in the intercellular delivery of misfolded proteins associated to neurodegenerative disorders, such as tau and amyloid β in Alzheimer's Disease (AD), α-synuclein in Parkinson's Disease (PD), superoxide dismutase (SOD)1 in amyotrophic lateral sclerosis and huntingtin in Huntington's Disease.
Mutant huntingtin induces a dominant, persistent nuclear rod phenotype similar to that described in Alzheimer's disease for cytoplasmic cofilin-actin rods.
Mutations in genes that cause inherited forms of Alzheimer's disease (amyloid precursor protein and presenilins), Parkinson's disease (alpha-synuclein and Parkin), and trinucleotide repeat disorders (huntingtin, androgen receptor, ataxin, and others) overwhelm endogenous neuroprotective mechanisms; other genes, such as those encoding apolipoprotein E(4), have more subtle effects on brain aging.
Huntingtin is found in areas of the brain that degenerate in this disease but is also associated with pathogenic inclusions in Alzheimer disease and Pick disease.