Genetic and pharmacologic p32-inhibition rescue CHCHD2-linked Parkinson's disease phenotypes in vivo and in cell models.

Background: Mutations in CHCHD2 have been linked to Parkinson's disease, however, their exact pathophysiologic roles are unclear. The p32 protein has been suggested to interact with CHCHD2, however, the physiological functions of such interaction in the context of PD have not been clarified.

Methods: Interaction between CHCHD2 and p32 was confirmed by co-immunoprecipitation experiments.

Varied pathological and therapeutic response effects associated with CHCHD2 mutant and risk variants.

Mutations and polymorphic risk variant of coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2) have been associated with late-onset Parkinson disease. In vivo pathological evidence of CHCHD2 mutations is currently lacking. Utilizing transgenic Drosophila model, we examined the relative pathophysiologic effect of the pathogenic (c.

FUS-linked essential tremor associated with motor dysfunction in Drosophila.

Essential tremor (ET) is one of the most common adult-onset neurological disorders which produce motor and non-motor symptoms. To date, there are no gold standard pathological hallmarks of ET, and despite a strong genetic contribution toward ET development, only a few pathogenic mutations have been identified. Recently, a pathogenic FUS-Q290X mutation has been reported in a large ET-affected family; however, the pathophysiologic mechanism underlying FUS-linked ET is unknown.