Treatments that elevate the protein, known as ubiquitin C-terminal hydrolase L1 (Uch-L1), might therefore have potential as a new therapy for Alzheimer's disease, according to the researchers. Currently available therapies have almost exclusively targeted amyloid beta (Aß), the protein responsible for the "amyloid plaques" that riddle the brains of patients with Alzheimer's disease, they added.
"By injecting what is essentially a Uch-L1 drug to raise its levels in the brain, we were able to restore a great deal of brain activity in a transgenic mouse model of Alzheimer's disease," said Michael Shelanski of Columbia University.
"While amyloid beta is certainly a key player in Alzheimer's disease--and efforts to reduce it remain a worthy goal--our results show that, even in the presence of the plaque, damage to memory can be reversed."
The findings suggest that neurons' protein-ridding machinery, the so-called ubiquitin/proteasomal pathway, may play an important early role in the pathogenesis of Alzheimer's disease, he added.
Ubiquitin is a "tag" that marks proteins for destruction by the cellular "garbage disposal" known as the proteasome, Shelanski explained. Uch-L1 acts as the proteasome's "gatekeeper," he added. Before proteins can be eliminated by the proteasome, Uch-L1 must remove their ubiquitin tag.
Earlier studies found that the brains of Alzheimer's disease patients show an accumulation of ubiquitin-tagged proteins, suggesting some defect of the protein degradation machinery, the researchers noted. Studies o