The tau hypothesis

The low-molecular-weight microtubule-associated protein, tau, has been implicated in the pathophysiology of AD and other CNS neurodegenerative diseases for which dementia and NFT formation is a common feature (e.g., FTDP linked to chromosome 17 (FTDP-17); Niemann-Pick disease type C).19 Tau plays an important role in axonal transport, stabilizing microtubules, a process regulated by phosphorylation at one or more of the 30 identified serine and threonine sites on the protein. Kinases known to phosphorylate tau include microtubule affinity-regulating kinase, cyclin-dependent kinase-5 (CDK-5), glycogen synthase kinase-3 (GSK-3), c-jun N-terminal kinase (JNK), protein kinase A, protein kinase C, and calcium/calmodulin-dependent protein kinase II. Dephosphorylation of tau occurs via protein phosphatase-1, -2A, and -2B activity as well as the prolyl isomerase, Pin 1. In pathological states, tau is hyperphosphorylated, which causes its dissociation from microtubules and aggregation into a fibrillar form, paired helical filaments, which further aggregate to constitute the NFT. In AD, dementia is more closely correlated with NFT formation than amyloid plaques; thus, mechanisms involved in NFT formation have been of interest for drug development, with selective kinase inhibitors and inhibitors of tau protein aggregation being potential targets.

Diabetes Sustenance

Diabetes Sustenance

Get All The Support And Guidance You Need To Be A Success At Dealing With Diabetes The Healthy Way. This Book Is One Of The Most Valuable Resources In The World When It Comes To Learning How Nutritional Supplements Can Control Sugar Levels.

Get My Free Ebook


Post a comment