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CDK5 and GSK3 mediate neuroinflammation-induced neurodegeneration

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive paralysis resulting from specific degeneration of upper and lower motor neurons (MNs). Chronic neuroinflammation, mediated by activated microglia, is a hallmark of patients diagnosed with ALS, and correlates with disease pathogenesis. Protecting MNs, particularly from toxic insults caused by neuroinflammation, could lead to effective treatments of ALS patient. Here, we report a screening campaign identifying a series of pyrazolotriazines that cell-autonomously protect MNs against neuroinflammation. We demonstrate that these compounds inhibit Cyclin-dependent kinase 5 (CDK5) and Glycogen synthase kinase 3 (GSK3), and we use phospho-proteomics to show that neuroprotection is linked to alterations in microtubule dynamics.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Motor Neuron

DISEASE(S): Amyotrophic Lateral Sclerosis

SUBMITTER: Hannes Drexler

LAB HEAD: Hannes C. A. Drexler

PROVIDER: PXD006452 | Pride | 2019-01-30

REPOSITORIES: pride

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	20151124_exp0722_Lydia_12-9_300NO_1_01.raw	Raw
	20151124_exp0722_Lydia_12-9_300NO_1_02.raw	Raw
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	20151124_exp0722_Lydia_12-9_300NO_1_05.raw	Raw

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