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89 results about "Neuronal degeneration" patented technology

Neuronal Degeneration. An inherited neurological disease, called “Neuronal Degeneration” or NDG, has been reported in Great Pyrenees dogs. The age-of-onset of this disease is very young, well before an affected dog’s first birthday, but begins quite mildly. Initial signs include slipping, sliding, and difficulty maneuvering on smooth surfaces.

Leucine-rich repeat kinase (LRRK2) drosophila model for parkinson's disease: wildtype1 (WT1) and G2019S mutant flies

Mutations in the leucine-rich repeat kinase (LRRK2) gene cause late-onset autosomal dominant Parkinson's disease (PD) with pleiomorphic pathology. Previously, we and others found that expression of mutant LRRK2 causes neuronal degeneration in cell culture. Here we used the GAL4/UAS system to generate transgenic Drosophila expressing either wild-type (WT1) human LRRK2 or LRRK2-G2019S, the most common mutation associated with PD. Expression of either WT1 human LRRK2 or LRRK2-G2019S in the photoreceptor cells caused retinal degeneration. Expression of WT1 LRRK2 or LRRK2-G2019S in neurons produced adult-onset selective loss of dopaminergic neurons, locomotor dysfunction, and early mortality. Expression of mutant G2019S-LRRK2 caused a more severe parkinsonism-like phenotype than expression of equivalent levels of WT1 LRRK2. Treatment with L-DOPA improved mutant LRRK2-induced locomotor impairment but did not prevent the loss of tyrosine hydroxylase (TH)-positive neurons. To our knowledge, this is the first in vivo “gain-of-function” model which recapitulates several key features of LRRK2-linked human parkinsonism. These flies may provide a useful model for studying LRRK2-linked pathogenesis and for future therapeutic screens for PD intervention.
Owner:THE JOHN HOPKINS UNIV SCHOOL OF MEDICINE
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