Alzheimer?s disease (AD) is a neurodegenerative disorder caused by progressive loss of synapses and neurons, characterized
by memory dysfunction and global cognitive impairment. The pathological hallmarks for AD are extracellular senile plaques
of amyloid-β-peptide (Aβ) and intracellular neurofibrillary tangles (NFTs) of hyper-phosphorylated tau protein. Tau inclusions
are not found only in Alzheimer?s disease but in many others neurodegenerative diseases. Their accumulation in neurons as
ubiquitinated filaments suggests a failure in the degradation limb of the Tau pathway. The components of a Tau protein triage
system consisting of CHIP/Hsp70 and other chaperones have begun to emerge. However, the site of triage and the master
regulatory elements are unknown. Here we report an elegant mechanism of Tau degradation involving the co-chaperone BAG2.
The BAG2/Hsp70 complex is tethered to the microtubule and this complex can capture and deliver Tau to the proteasome for
ubiquitin-independent degradation. This complex preferentially degrades toxic Tau. Thus we propose that ubiquitinated Tau
inclusions arise due to shunting of Tau degradation toward a less efficient ubiquitin-dependent pathway
Daniel Carneiro Carrettiero has completed his Ph.D at the age of 31 years from University of S?o Paulo (USP) in 2008. He was in UCSB, Santa
Barbara, as visiting scientist in 2008 in Kosik?s lab. He also performed his postdoctoral studies in the same university in Brasil. Now, he is a
associated professor in a Federal University / Santo Andr? / S?o Paulo / Brasil.
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