The therapeutic potentials of quercetin against neurotoxicity

Alzheimer's Disease: Status of Low‐Dimensional Nanotherapeutic Materials

“…Subsequently, 𝛾-secretase performs another cleavage at the C-terminus, producing A𝛽1-40 and A𝛽1-42. [42][43][44][45][46] Such the intracellular cleavage of APP by the proteolytic enzymes 𝛽-secretase and 𝛾-secretase produces the short peptide known as A𝛽 with 40-42 amino acids, of which the A𝛽1-40 is the major species and the A𝛽1-42 is the most fibrillogenic and predominant component in AD plaques. [45] Besides, gene mutations also increase the production of A𝛽.…”

“…[39,[47][48][49][50][51][52] The differential lipidation status exhibited by apolipoprotein E (ApoE) isoforms such as ApoE4 (E4), ApoE3 (E3), and ApoE2 regulates A𝛽's accumulation and lessens its clearance by stimulating cellular uptake and degradation of ApoE-A𝛽 complexes from the brain (E4 > E3 and E2). [46] The accumulation of toxic A𝛽 induced by the imbalance of production and elimination can damage neurons and synapses in the brain through various mechanisms. They include the upregulation of the receptor for advanced glycation end products (RAGE) leading to neurotoxicity.…”

“…[93][94] Other mentals like Fe 3+ , Mn 2+ , Pb 2+ , Cd 2+ , Hg 2+ , and Al 3+ also stimulate amyloidogenic pathways and A𝛽 aggregation. [46] Excessive levels of transition-metal ions reacting with oxygen such as Cu 2+ can catalyze the generation of cytotoxic ROS and thereafter induce neuronal cell apoptosis. [75,95] Nevertheless, due to the limited understanding of the precise involvement of metal dyshomeostasis and its interaction with other pathological factors, it is crucial to propose effective metal chelation therapy as a mean to restore homeostasis in Alzheimer's disease (AD).…”