Alzheimer's Disease: A Molecular View of β-Amyloid Induced Morbific Events

Amyloid-beta (A beta) is a dynamic peptide of Alzheimer's disease (AD) which accelerates the disease progression. At the cell membrane and cell compartments, the amyloid precursor protein (APP) undergoes amyloidogenic cleavage by beta- and gamma-secretases and engenders the A beta. In addition, externally produced A beta gets inside the cells by receptors mediated internalization. An elevated amount of A beta yields spontaneous aggregation which causes organelles impairment. A beta stimulates the hyperphosphorylation of tau protein via acceleration by several kinases. A beta travels to the mitochondria and interacts with its functional complexes, which impairs the mitochondrial function leading to the activation of apoptotic signaling cascade. A beta disrupts the Ca2+ and protein homeostasis of the endoplasmic reticulum (ER) and Golgi complex (GC) that promotes the organelle stress and inhibits its stress recovery machinery such as unfolded protein response (UPR) and ER-associated degradation (ERAD). At lysosome, A beta precedes autophagy dysfunction upon interacting with autophagy molecules. Interestingly, A beta act as a transcription regulator as well as inhibits telomerase activity. Both A beta and p-tau interaction with neuronal and glial receptors elevate the inflammatory molecules and persuade inflammation. Here, we have expounded the A beta mediated events in the cells and its cosmopolitan role on neurodegeneration, and the current clinical status of anti-amyloid therapy.

Automated summary

Amyloid-beta (Aβ) plays a crucial role in Alzheimer's disease progression by affecting cellular structures and functions through various mechanisms, ultimately leading to neurodegeneration.