Importance of the subcellular location of protein deposits in neurodegenerative diseases

Alzheimer's disease, Parkinson's, Huntington's, amyotrophic lateral sclerosis (ALS) and prion disorders are devastating neurodegenerative diseases of increasing prevalence in aging populations. Although clinically different, they share similar molecular features: the accumulation of one or two proteins in abnormal conformations inside or outside neurons. Enhancing protein quality control systems could be a useful strategy to neutralize the abnormal proteins causing neurodegenerative diseases. This review emphasizes the subcellular location of protein deposits in neurodegenerative diseases and the need to tailor strategies aimed at boosting protein quality control systems to the affected subcellular compartment. Inhibition of a protein phosphatase terminating the unfolded protein response will be discussed as a strategy to protect from diseases associated with misfolded proteins in the endoplasmic reticulum.