Mitochondrial Alterations, Oxidative Stress and Neuroinflammation in Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is a multifactorial disorder characterized by the progressive deterioration of neuronal networks. The primary cause and sequence of its progression are only partially understood but abnormalities in folding and accumulation of insoluble proteins such as p-amyloid and Tau-protein are both associated with the pathogenesis of AD. Mitochondria play a crucial role in cell survival and death, and changes in mitochondrial structure and/or function are related to many human diseases. Increasing evidence suggests that compromised mitochondrial function contributes to the aging process and thus may increase the risk of AD. Dysfunctional mitochondria contribute to reactive oxygen species which can lead to extensive macromolecule oxidative damage and the progression of amyloid pathology. Oxidative stress and amyloid toxicity leave neurons chemically vulnerable. The mitochondrial toxicity induced by p-amyloid is still not clear but may include numerous mechanisms, such as the increased permeability of mitochondrial membranes, the disruption of calcium homeostasis, the alteration of oxidative phosphorylation with a consequent overproduction of reactive oxygen species. Other mechanisms have been associated with the pathophysiology of AD. Inflammatory changes are observed in AD brain overall, particularly at the amyloid deposits, which are rich in activated microglia. Once stimulated, the microglia release a wide variety of pro-inflammatory mediators including cytokines, complement components and free radicals, all of which potentially contribute to further neuronal dysfunction and eventually death. Clinically, novel approaches to visualize early neuroinflammation in the human brain are needed to improve the monitoring and control of therapeutic strategies that target inflammatory and other pathological mechanisms. Similarly, there is growing interest in developing agents that modulate mitochondrial function.Alzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by a progressive deterioration of cognitive functions with consequent reduction of memory, associated with a decrease in

Nootropic, neuroprotective and neurotrophic effects of phloretin in scopolamine induced amnesia in mice

“…In addition to this, 7 days SCP administration has found to increase neuroinflammatory markers like nuclear factor-κB and tumor necrosis factor-αmediated tissue injury in the hippocampus (Jang et al, 2013). This further causes induction of neuroinflammation which viciously leads to substantial increase in oxidative stress (Verri et al, 2012). Additionally, SCP also interferes with the neurotrophic factor, BDNF regulation by down-regulating it (da Penha Berzaghi et al, 1993).…”

Genetic variation of oxidative phosphorylation genes in stroke and Alzheimer's disease

“…Previously accumulated evidence has implicated the OXPHOS system in AD onset and progression (Eckert et al, 2010; Horan et al, 2012; Morán et al, 2012; Rhein et al, 2009; Schmitt et al, 2012; Verri et al, 2012). Our GSEA identified associations between SNPs within OXPHOS genes and clinical status, providing evidence that common variation within the 105 genes directly contributing structural proteins to the OXPHOS system is associated with the clinical manifestations leading from normal brain aging to AD.…”

Role of RAGE in Alzheimer’s Disease

“…Emerging research studies note that neuroinflammation is a causable factor for the pathogenesis of AD, underlying enhancing the production of Ab (the formation of amyloid plaques) and the aberrant hyperphosphorylation of tau (the formation of NFTs) (Verri et al 2012;Faden and Loane 2014;Zhou et al 2014).…”