Title:G-Lymphatic, Vascular and Immune Pathways for Aβ Clearance Cascade and Therapeutic Targets For Alzheimer’s Disease
Volume: 24
Issue: 7
Author(s): Saurav Chakraborty, Jyothsna ThimmaReddygari and Divakar Selvaraj*
Affiliation:
- Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Ooty, Tamilnadu,India
Keywords:
Amyloid, Alzheimer`s disease, glymphatic pathway, RAGE, aquaporin 4, apolipoprotein E, clusterin.
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.
