Elevated p25 is thought to account for increased or pathological CDK5 activation that seems to be a commonality in several human neurodegenerative diseases. However, it is not yet understood how so many different etiologies lead to this common step in CDK5 activation, or how CDK5 participates in the unique pathological landscapes in the different diseases. Although it is widely accepted that environmental factors play a significant role in regulating the onset and progression of neurodegenerative diseases, this study by Kitazawa et al. provides tangible evidence for a link between inflammation and p25-induced CDK5 activation in the triple transgenic AD mouse.

Curiously, activation of CDK5 by the inflammatory agent lipopolysaccharide (LPS) had no impact on amyloid pathology but enhanced phosphorylation of tau at specific sites. This enhanced phosphorylation of tau was blocked by the pan-CDK inhibitor, roscovitine, supporting the idea that LPS-induced tau hyperphosphorylation is mediated by CDK5. This study opens the way to exploring a wide variety of immune-mediated mechanisms...  Read more

Elevated p25 is thought to account for increased or pathological CDK5 activation that seems to be a commonality in several human neurodegenerative diseases. However, it is not yet understood how so many different etiologies lead to this common step in CDK5 activation, or how CDK5 participates in the unique pathological landscapes in the different diseases. Although it is widely accepted that environmental factors play a significant role in regulating the onset and progression of neurodegenerative diseases, this study by Kitazawa et al. provides tangible evidence for a link between inflammation and p25-induced CDK5 activation in the triple transgenic AD mouse.

Curiously, activation of CDK5 by the inflammatory agent lipopolysaccharide (LPS) had no impact on amyloid pathology but enhanced phosphorylation of tau at specific sites. This enhanced phosphorylation of tau was blocked by the pan-CDK inhibitor, roscovitine, supporting the idea that LPS-induced tau hyperphosphorylation is mediated by CDK5. This study opens the way to exploring a wide variety of immune-mediated mechanisms in regulation of brain CDK5 activity and perhaps neurodegenerative pathology. Because of the broad specificity of roscovitine, molecular identification of the relevant CDK(s) will need to be pursued.

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