Recent approaches targeting Beta-amyloid for therapeutic intervention of Alzheimer's disease.

摘要

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neuropathological features comprising amyloid deposits and neuronal losses in brain. In AD, aggregation of a beta amyloid peptide (Abeta), produced from proteolytic cleavage of amyloid precursor protein, is believed to be implicated in the pathophysiological cascade leading to neuronal death. Most AD drugs currently available can only alleviate symptoms rather than modify the underlying molecular cause of AD. In this review, we describe and discuss the recent patents issued within the past two years focusing on therapeutic interventions targeting at various Abeta-associated pathological mechanisms of AD. The described therapeutic strategies include 1) reduction of synthesis of Abeta, 2) inhibition of Abeta aggregation, 3) immunotherapeutic/enzymatic clearance of Abeta, 4) targeting other amyloidogenic proteins interacting with Abeta and 5) amelioration of Abeta downstream toxic effects. Important issues to be considered for further improvement of therapeutic efficacy of these approaches are also discussed.