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Parkinson_s_Disease_08 - – Mutated α-synuclein produced...

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Parkinson’s Disease In North America about 1M affected 50,000 new cases/year Median age of onset 60 years Loss of Dopaminergic cells of the Substantia Nigra Symptoms appear when >50% of the cells die 95% sporadic, 5% genetic
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Symptoms Resting tremor in the hands Rigidity Slow movement Impaired balance and gait Expressionless face
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Pathology Cell stress Misfolded proteins congregate Intracellular protein clumps are called Lewy Bodies Chaperones start refolding proteins Protein elimination through ubiquitin- proteasome system Ubiquitin system overwhelmed, toxic proteins accumulate, cells die
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Genetic Mutations Alpha-synuclein
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Unformatted text preview: – Mutated α-synuclein produced in large amounts causes degeneration of dopaminergic neurons – Folds incorrectly and accumulates in Lewy Bodies • Mutant parkin – Failure of the ubiquitin system to dispose abnormal proteins Treatment • L-Dopa • Deep brain stimulation • Stem cell transplants: functional benefit modest despite 100K surviving dopaminergic cells • Gene therapy to inhibit overactive regions (subthalmic nucleus) • Increasing chaperone activity in S. Nigra • Glial derived neurotrophic factor (GDNF) Lozano and Kalia, Sci. Am., July, 2005 Lozano and Kalia, Sci. Am.,July, 2005...
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