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

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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

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The Alzheimer disease is a age related neurodegenerative disease. The factors causing alzheimer disease are numerous. Research on humans and rodent models predicted various causative factors involved in Alzheimer disease progression. Among them, neuroinflammation, oxidative stress and apoptosis play a major role because of 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 have a major role in Alzheimer 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 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 neurodegenerative cascade and neuronal cell death occurs. Studies had shown disturbed sleep may be a risk factor for dementia and cognitive decline. In this review, the therapeutic targets for alzheimer disease via focussing on pathways for amyloid beta clearance are discussed.

Keywords: Amyloid, Alzheimer disease, Glymphatic pathway, RAGE, Aquaporin 4, Apolipoprotein E and Clusterin.

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(E-pub Ahead of Print)
DOI: 10.2174/1386207323666200901095003
Price: $95

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