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. 2013:2013:413808.
doi: 10.1155/2013/413808. Epub 2013 May 15.

Amyloidosis in Alzheimer's Disease: The Toxicity of Amyloid Beta (A β ), Mechanisms of Its Accumulation and Implications of Medicinal Plants for Therapy

Anchalee Prasansuklab  1 , Tewin Tencomnao
Affiliations

Amyloidosis in Alzheimer's Disease: The Toxicity of Amyloid Beta (A β ), Mechanisms of Its Accumulation and Implications of Medicinal Plants for Therapy

Anchalee Prasansuklab et al. Evid Based Complement Alternat Med. 2013.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that leads to memory deficits and death. While the number of individuals with AD is rising each year due to the longer life expectancy worldwide, current therapy can only somewhat relieve the symptoms of AD. There is no proven medication to cure or prevent the disease, possibly due to a lack of knowledge regarding the molecular mechanisms underlying disease pathogenesis. Most previous studies have accepted the "amyloid hypothesis," in which the neuropathogenesis of AD is believed to be triggered by the accumulation of the toxic amyloid beta (A β ) protein in the central nervous system (CNS). Lately, knowledge that may be critical to unraveling the hidden pathogenic pathway of AD has been revealed. This review concentrates on the toxicity of A β and the mechanism of accumulation of this toxic protein in the brain of individuals with AD and also summarizes recent advances in the study of these accumulation mechanisms together with the role of herbal medicines that could facilitate the development of more effective therapeutic and preventive strategies.

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Figures

Figure 1
Figure 1
Proteolytic processing of amyloid precursor protein (APP). Amyloid precursor protein (APP) is a ubiquitously expressed integral membrane protein that can be processed in two distinct pathways. In the nonamyloidogenic pathway, APP is cleaved within the Aβ domain by the α-secretase enzyme. However, in the amyloidogenic pathway, APP is first cleaved by β-secretase (BACE1), instead of α-secretase, at the N-terminus of the Aβ domain, and this is followed by γ-secretase cleavage at the C-terminus. This sequence of events generates the Aβ amylogenic peptides, which can aggregate into oligomers and form extracellular neurotoxic plaques in the brain. Both pathways release identical APP intracellular C-terminal domain (AICD). This figure was adapted from Thinakaran and Koo (2008) [11].
Figure 2
Figure 2
Schematic diagram of Aβ accumulation mechanism. This schematic diagram summarizes the factors influencing Aβ accumulation and the molecular mechanisms involved in the pathways for overproduction and impaired clearance of toxic Aβ peptides. Several potential targets for AD treatment, such as AChE, LRP1, and RAGE, and certain components involved in the control of cerebral blood flow and the autophagic pathway are suggested by their direct involvement in Aβ accumulation mechanism.
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