Current advances in the treatment of Alzheimer's disease: focused on considerations targeting Aβ and tau

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder that impairs mainly the memory and cognitive function in elderly. Extracellular beta amyloid deposition and intracellular tau hyperphosphorylation are the two pathological events that are thought to cause neuronal dysfunction in AD. Since the detailed mechanisms that underlie the pathogenesis of AD are still not clear, the current treatments are those drugs that can alleviate the symptoms of AD patients. Recent studies have indicated that these symptom-reliving drugs also have the ability of regulating amyloid precursor protein processing and tau phosphorylation. Thus the pharmacological mechanism of these drugs may be too simply-evaluated. This review summarizes the current status of AD therapy and some potential preclinical considerations that target beta amyloid and tau protein are also discussed.

Inhibition of glycogen synthase kinase-3β enhances cognitive recovery after stroke: the role of TAK1

“…Loss of GSK-3b, not GSK-3a, suppressed spontaneous neuronal death in extended culture models (Liang and Chuang 2007). Nonselective GSK-3b inhibition with lithium is neuroprotective (Chuang et al 2011;Wei et al 2013) and GSK-3b inhibitors are currently being tested in clinical trials for treatment of cognitive deficits and dementia (Hong-Qi et al 2012). GSK-3b is known to interact with the mitogen-activated protein kinase family (MAPKs) and promotes signaling after stress (Kim et al 2003).…”

Chemical and Physical Approaches for the Treatment of Alzheimer's Disease

“…The inhibitors of CDK5 seem to impair the development of pathology in tau transgenic mice [90]. The M1 muscarinic agonist AF267B (NGX267) can inhibit GSK-3β [1]. Also, minocycline could inhibit tau aggregation, which associated with the suppression of Aβ-induced neuronal death and cognitive impairment in animal models [91].…”

“…Several proteinases, such as, neprilysin (NEP) [70,71], angiotensin-converting enzyme (ACE) [1], plasmin [1], insulin degrading enzyme (IDE) [1], and endothelin converting enzyme (ECE) 1 and 2 [1], were shown to be able to degrade Aβ peptides in vitro or in animal models.…”

“…A growing number of people suffer from AD due to the aggravation of social aging and the dilation of average life expectancy, which brings about heavy burden to the families, the society and the whole world [1]. Therefore numerous researchers and clinicians have spent considerable effort to find a cure.…”

“…Aβ42 is predominant in the brain parenchyma of AD patients, which may result from fibrillogenic feature. If Aβ cascade is chosen as therapeutic target, four main options seem to be feasible to tackle the problem: (1) suppression of Aβ production, (2) stimulation of Aβ clearance, (3) prevention of Aβ aggregation into amyloid plaques, and (4) raising brain resistance to Aβ [1,13]. …”