Diverse molecular targets for therapeutic strategies in Alzheimer's disease

Abstract

Alzheimer's disease (AD) is the most common form of dementia caused by neurodegenerative process and is tightly related to amyloid β (Aβ) and neurofibrillary tangles. The lack of early diagnostic biomarker and therapeutic remedy hinders the prevention of increasing population of AD patients every year. In spite of accumulated scientific information, numerous clinical trials for candidate drug targets have failed to be preceded into therapeutic development, therefore, AD-related sufferers including patients and caregivers, are desperate to seek the solution. Also, effective AD intervention is desperately needed to reduce AD-related societal threats to public health. In this review, we summarize various drug targets and strategies in recent preclinical studies and clinical trials for AD therapy: Allopathic treatment, immunotherapy, Aβ production/aggregation modulator, tau-targeting therapy and metabolic targeting. Some has already failed in their clinical trials and the others are still in various stages of investigations, both of which give us valuable information for future research in AD therapeutic development.

Keywords: Aggregation; Alzheimer Disease; Amyloid Beta-Peptides; Glucose Metabolism; Immunotherapy; Tau Protein.

Fig. 1

Diverse AD therapeutic strategies and their example chemicals tested in pre-clinical or clinical studies. APP, Amyloid precursor protein; Aβ, Amyloid β; QC, Glutaminyl cyclase; AchEI, Acetylcholinesterase inhibitors; nAchRc, Nicotinic acetylcholine receptor; 5-HT6 Rc, 5-hydroxytryptamine 6 receptor; NSAIDS, Nonsteroidal anti-inflammatory drugs; O-GlcNAc, O-linked β-N-acetylglucosamine; NButGT, 1, 2-dideoxy-2'-propyl-α-D-glucopyranoso-[2,1-d]-Δ2'-thiazoline; HDAC, Histone deacetylation.