Challenges in the treatment of Alzheimer's disease: recent progress and treatment strategies of pharmaceuticals targeting notable pathological factors

Abstract

Introduction: Alzheimer's disease (AD), a commonly encountered neurodegenerative disorder, causes cognitive decline and has a devastating effect on the quality of life. AD occurs mainly through abnormal amyloid β peptide (Aβ) and tau protein (tau) activity around/in neurons. Aβ-based therapeutic techniques have been struggled to treat AD over the past few decades. In addition, the complexity in treating AD is due to diverse factors regulating its pathology. Areas covered: This review emphasizes recent advances regarding various pathological approaches and provides an overview of the most recent medications for AD. The authors focus on the regulatory factors, which mediate AD pathology, and discuss a variety of newly developed drugs and compounds used to inhibit β-secretase and γ-secretase activity, remove oligomeric Aβ and aggregated Aβ that is given responsibility in the amyloid cascade hypothesis, prevent tau hyperphosphorylation, restrain phosphorylated tau (p-tau) aggregation, remove aggregated p-tau that is proposed in tauopathy, and other related pathways. Expert opinion: The approaches to the treatment of AD towards Aβ and tau have failed in most clinical attempts due to insufficient disease models arising from complex AD biology. It is the time to look for other approaches and pathological factors to cure AD.

Keywords: Alzheimer’s disease; amyloid cascade hypothesis; inhibitor; pathology; regulatory factor; tauopathy.