Amyloid beta plaque: a culprit for neurodegeneration.
Increasing life expectancy has resulted in an increase in neurodegenerative disorders like Alzheimer's disease. None of the hypothesis proposed till date explains the exact pathobiology of the disease. It is therefore imperative to understand the underlying mechanisms. Amyloid beta (Aβ) is regarded as the main culprit and maximum therapeutic efforts are centered towards Aβ. This review will discuss about the biosynthesis, the physiological role of Aβ including the pathogenic aggregation of Aβ resulting neurodegenerative cognitive disabilities. Most studies of Alzheimer's disease have focused on the biochemical mechanisms involved in the neurodegenerative processes triggered by Aβ aggregates. Aβ is generated from mature amyloid precursor protein being metabolized by two competing pathways, α-secretase pathway (non-amyloidogenic pathway) and β-secretase (amyloidogenic pathway). The physiological roles of Aβ reported in neurotrophic properties, neurogenesis, synaptic plasticity, metal ion sequestration and specificity of blood brain barrier. The neuronal injury is the result of Aβ oligomerization and it is reported that oligomerization of Aβ contributes to neurodegeneration in Alzheimer's disease. The physiological role of Aβ must be considered in the development of medications that intended to decrease its oligomerization forming plaques in a disease like Alzheimer's disease. The biosynthetic pathways for transport and accumulation of Aβ need to be ascertained as an attempt to develop future strategies for prevention of neurodegenerative disorders.
School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh, 173212, India.
Ankita
A
Gupta
School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh, 173212, India. rohit_pharm@yahoo.co.in.
Rohit
R
Goyal
D000544:Alzheimer Disease / Q000209:etiology* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000473:pathology*; D006801:Humans; D058225:Plaque, Amyloid / Q000473:pathology*
D016229:Amyloid beta-Peptides
Alzheimer; Amyloid; Cholesterol; Neurodegeneration