G-Lymphatic, Vascular and Immune Pathways for Aβ Clearance Cascade and Therapeutic Targets For Alzheimer’s Disease

Author(s): Saurav Chakraborty, Jyothsna ThimmaReddygari, Divakar Selvaraj*

Journal Name: Combinatorial Chemistry & High Throughput Screening
Accelerated Technologies for Biotechnology, Bioassays, Medicinal Chemistry and Natural Products Research

Volume 24 , Issue 7 , 2021


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Abstract:

Alzheimer's disease is an age-related neurodegenerative disease. The factors causing Alzheimer's disease are numerous. Research on humans and rodent models predicted various causative factors involved in Alzheimer's disease progression. Among them, neuroinflammation, oxidative stress, and apoptosis play a major role because of the accumulation of extracellular amyloid-beta peptides. Here, the clearance of amyloid beta-peptide plays a major role because of the imbalance in the production and clearance of the amyloid beta-peptide. Additionally, neuroinflammation by microglia, astrocytes, cytokines, chemokines, and the complement system also has a major role in Alzheimer's disease. The physiological clearance pathways involved in amyloid beta-peptide are glymphatic, vascular, and immune pathways. Amyloid precursor protein, low-density lipoprotein receptor-related protein 1, receptor for the advanced glycation end product, apolipoprotein E, clusterin, aquaporin 4, auto-antibodies, complement system, cytokines, and microglia are involved in amyloid beta-peptide clearance pathways across the blood-brain barrier. The plaque formation in the brain by alternative splicing of amyloid precursor protein and production of misfolded protein results in amyloid-beta agglomeration. This insoluble amyloid-beta leads to a neurodegenerative cascade and neuronal cell death occurs. Studies had shown that disturbed sleep may be a risk factor for dementia and cognitive decline. In this review, the therapeutic targets for Alzheimer'sdisease via focusing on pathways for amyloid-beta clearance are discussed.

Keywords: Amyloid, Alzheimer`s disease, glymphatic pathway, RAGE, aquaporin 4, apolipoprotein E, clusterin.

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Article Details

VOLUME: 24
ISSUE: 7
Year: 2021
Published on: 31 August, 2020
Page: [1083 - 1092]
Pages: 10
DOI: 10.2174/1386207323666200901095003
Price: $65

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