Expression of mutated huntingtin fragment in the putamen is sufficient to produce abnormal movement in non-human primates
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Animal models of human pathologies remain invaluable tools for unraveling disease mechanisms and evaluating potential therapeutic strategies. For a number of diseases, the lack of a reliable animal model represents an important limiting step towards the de ...
Here, we describe the selection and optimization of a chemical series active in both a full-length and a fragment-based Huntington's disease (HD) assay. Twenty-four thousand small molecules were screened in a phenotypic HD assay, identifying a series of co ...
While Parkinson's disease has been described nearly 200 years ago, the mechanisms leading to the degeneration of selectively vulnerable populations of neurons, such as dopaminergic neurons in the substantia nigra, remain mostly unknown. Our poor understand ...
Huntington's disease is an autosomal dominantly inherited neurodegenerative disorder characterized by progressive motor dysfunction, dementia, psychiatric symptoms, and weight loss, eventually leading to death. Postmortem analysis of the brains of HD patie ...
In spite of partial success in treating Parkinson's disease by using ectopically placed grafts of dopamine-producing cells, restoration of the original neuroanatomical circuits, if possible, might work better. Previous evidence of normal anatomic projectio ...
Aggravating aggregation: an N-terminal domain that is in close proximity to the polyQ domain in the huntingtin protein, htt105-138, is shown to be highly aggregation prone. Potential cross-talk between this domain and the polyQ region may play a central ro ...
Parkinson's disease is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. While sporadic in the majority of cases, PD-linked dominant mutations in the α-synuclein and LRRK-2 genes, and recess ...
Loss of function of parkin, an ubiquitin ligase, is responsible for autosomal recessive juvenile parkinsonism (AR-JP). Parkin-associated endothelin receptor-like receptor (Pael-R) was identified as an authentic substrate of parkin and is thought to accumul ...
Although previous studies of Huntington's disease (HD) have addressed many potential mechanisms of striatal neuron dysfunction and death, it is also known, based on clinical findings, that cortical function is dramatically disrupted in HD. With respect to ...
American Society for Pharmacology and Experimental Therapeutics2010
Parkinson's disease is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. While sporadic in the majority of cases. PD-linked dominant mutations in the a-synuclein and LRRK-2 genes, and recess ...