The Michael J. Fox Foundation for Parkinson's Research Strategy to Advance Therapeutic Development of PINK1 and Parkin.

The role of mitochondria in Parkinson's disease (PD) has been investigated since the 1980s and is gaining attention with recent advances in PD genetics research. Mutations in and PTEN-Induced Putative Kinase 1 () are well-established causes of autosomal recessive early-onset PD. Genetic and biochemical studies have revealed that PINK1 and Parkin proteins function together in the same biological pathway to govern mitochondrial quality control.

Basal and Evoked Neurotransmitter Levels in Parkin, DJ-1, PINK1 and LRRK2 Knockout Rat Striatum.

Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized by the loss of neurons in the substantia nigra that project to the striatum and release dopamine (DA), which is required for normal movement. Common non-motor symptoms likely involve abnormalities with other neurotransmitters, such as serotonin, norepinephrine, acetylcholine, glycine, glutamate and gamma-aminobutyric acid (GABA). As part of a broad effort to provide better PD research tools, the Michael J.

A Proposed Roadmap for Parkinson's Disease Proof of Concept Clinical Trials Investigating Compounds Targeting Alpha-Synuclein.

The convergence of human molecular genetics and Lewy pathology of Parkinson's disease (PD) have led to a robust, clinical-stage pipeline of alpha-synuclein (α-syn)-targeted therapies that have the potential to slow or stop the progression of PD and other synucleinopathies. To facilitate the development of these and earlier stage investigational molecules, the Michael J. Fox Foundation for Parkinson's Research convened a group of leaders in the field of PD research from academia and industry, the Alpha-Synuclein Clinical Path Working Group.

Large-scale phenome analysis defines a behavioral signature for Huntington's disease genotype in mice.

Rapid technological advances for the frequent monitoring of health parameters have raised the intriguing possibility that an individual's genotype could be predicted from phenotypic data alone. Here we used a machine learning approach to analyze the phenotypic effects of polymorphic mutations in a mouse model of Huntington's disease that determine disease presentation and age of onset. The resulting model correlated variation across 3,086 behavioral traits with seven different CAG-repeat lengths in the huntingtin gene (Htt).

Animal models of Huntington's disease for translation to the clinic: best practices.

Mouse models of Huntington's disease (HD) recapitulate many aspects of the human disease. These genetically modified mice are powerful tools that are used not only to examine the pathogenesis of the disease, but also to assess the efficacy of potential new treatments. Disappointingly, in the past few years we have seen the success of potential therapies in animal studies, subsequently followed by failure in clinical trials.