Apoptosis in Alzheimer’s Disease: An Understanding of the Physiology, Pathology and Therapeutic Avenues

Abstract

Alzheimer's disease (AD) is a devastative neurodegenerative disorder with complex etiology. Apoptosis, a biological process that plays an essential role in normal physiology to oust a few cells and contribute to the normal growth, when impaired or influenced by various factors such as Bcl2, Bax, caspases, amyloid beta, tumor necrosis factor-α, amyloid precursor protein intracellular C-terminal domain, reactive oxygen species, perturbation of enzymes leads to deleterious neurodegenerative disorders like AD. There are diverse pathways that provoke manifold events in mitochondria and endoplasmic reticulum (ER) to execute the process of cell death. This review summarizes the crucial apoptotic mechanisms occurring in both mitochondria and ER. It gives substantial summary of the diverse mechanisms studied in vivo and in vitro. A brief account on neuroprotection of several bioactive components, flavonoids and antioxidants of plants against apoptotic events of both mitochondria and ER in both in vitro and in vivo has been discussed. In light of this, the burgeoning need to develop animal models to study the efficacy of various therapeutic effects has been accentuated.

Novel Compounds Targeting the Mitochondrial Protein VDAC1 Inhibit Apoptosis and Protect against Mitochondrial Dysfunction

“…Specifically, we sought anti-apoptotic drugs targeting VDAC1 to prevent its oligomerization, an early and critical step in the progression of apoptosis. These molecules would be potential candidates for treating neurodegenerative disorders (16,17) and various cardiovascular diseases, where enhanced apoptosis also occurs (48 -50).…”

“…This leads to the activation of caspases, which cleave targeted proteins, and subsequently to apoptosis. Defects in the regulation of apoptosis are associated with cancer and neurodegenerative diseases (14), with evasion of apoptosis being a hallmark of cancer (15) and enhancement of apoptosis being seen in neurodegenerative diseases (16,17).…”

Luteinizing hormone as a key player in the cognitive decline of Alzheimer's disease

“…Cortical and hippocampal degradation is precipitated and accompanied by a number of cellular and molecular markers associated with Alzheimer's disease pathology. These include abnormally hyper-phosphorylated neurofibrillary tau tangles, amyloid beta (Aβ) plaque deposits, and neuronal cell death (Niikura et al, 2002;Obulesu and Lakshmi, 2014). There is also decreased neurogenesis and plasticity in hippocampal and cortical regions (Gandy and Dekosky, 2013;Iqbal and Grundke-Iqbal, 2011;Revett et al, 2013) concomitant with decreased levels of the neurotrophic factor BDNF, a key modulator of synaptic plasticity (Palm et al, 2014;Phillips et al, 1991).…”

Antiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron overload

“…Studies have consistently reported deregulations in the expression of apoptotic proteins in the brains of both PD and AD patients and in experimental models of neurodegenerative disorders (for a review, see 19,20 ). Among the stimuli known to trigger apoptosis are alterations of the redox balance and oxidative damage 21,22 .…”