Research ArticleParkinson’s Disease

Nigral dopaminergic PAK4 prevents neurodegeneration in rat models of Parkinson’s disease

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Science Translational Medicine  30 Nov 2016:
Vol. 8, Issue 367, pp. 367ra170
DOI: 10.1126/scitranslmed.aaf1629

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PAKing a punch in Parkinson’s disease

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and is caused by the loss of dopaminergic (DA) neurons in the substantia nigra. The resulting decrease in dopamine leads to resting tremor and rigidity in patients with this disease. PAK4 (p21-activated kinase 4) is known to play a key role in neuronal survival. Now, Won et al. show that constitutively active PAK4S445N/S474E protects DA neurons from neurodegeneration in two rodent models of PD. The neuroprotective effect of constitutively active PAK4 required CREB and its brain-specific coactivator CRTC1. These findings may provide an avenue for developing neuroprotective interventions for PD.