Selective Neuronal Death in Neurodegenerative Diseases: The Ongoing Mystery

A major unresolved problem in neurodegenerative disease is why and how a specific set of neurons in the brain are highly vulnerable to neuronal death. Multiple pathways and mechanisms have been proposed to play a role in Alzheimer disease (AD dagger), Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington disease (HD), yet how they contribute to neuronal vulnerability remains far from clear. In this review, various mechanisms ascribed in AD, PD, ALS, and HD will be briefly summarized. Particular focus will be placed on Rhes-mediated intercellular transport of the HD protein and its role in mitophagy, in which I will discuss some intriguing observations that I apply to model striatal vulnerability in HD. I may have unintentionally missed referring some studies in this review, and I extend my apologies to the authors in those circumstances.