Apoptosis and Oxidative Stress in Neurodegenerative Diseases

Abstract

Neurodegenerative disorders affect almost 30 million individuals leading to disability and death. These disorders are characterized by pathological changes in disease-specific areas of the brain and degeneration of distinct neuron subsets. Despite the differences in clinical manifestations and neuronal vulnerability, the pathological processes appear similar, suggesting common neurodegenerative pathways. Apoptosis seems to play a key role in the progression of several neurologic disorders like Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis as demonstrated by studies on animal models and cell lines. On the other hand, research on human brains reported contradictory results. However, many dying neurons have been detected in brains of patients with neurodegenerative diseases, and these conditions are often associated with significant cell loss accompanied by typical morphological features of apoptosis such as chromatin condensation, DNA fragmentation, and activation of cysteine-proteases, caspases. Cell death and neurodegenerative conditions have been linked to oxidative stress and imbalance between generation of free radicals and antioxidant defenses. Multiple sclerosis, stroke, and neurodegenerative diseases have been associated with reactive oxygen species and nitric oxide. Here we present an overview of the involvement of neuronal apoptosis and oxidative stress in the most important neurodegenerative diseases, mainly focusing the attention on several genetic disorders, discussing the interaction between primary genetic abnormalities and the apoptotic pathways.

Pathway of 3-MCPD-induced apoptosis in human embryonic kidney cells

“…The most common and well-defined form of programmed cell death is apoptosis, which is a physiological cell-suicide pro-gramme that is essential for embryonic development (Campos-Ortega and Hartenstein, 2013), immune-system function (Abbas et al, 2012) and the maintenance of tissue homeostasis (Sonnenberg et al, 2011) in multi-cellular organisms. Deregulation of apoptosis has been implicated in numerous pathological conditions, including neurodegenerative diseases (Radi et al, 2014), autoimmunity and cancer (Rabinovich and Croci, 2012).…”

Cerebral Oxidative Stress and Microvasculature Defects in TNF-α Expressing Transgenic and Porphyromonas gingivalis-Infected ApoE–/– Mice

“…Prolonged episodes of oxidative stress produces an excessive accumulation of reactive oxygen species (ROS), capable of inducing deleterious cellular and biomolecular damage to the host [1][2][3][4][5]. Neurons are particularly sensitive to ROSmediated, oxidative damage, as they contain higher numbers of mitochondria along their cell bodies and axonal/dendritic tree lengths, compared to other cell types.…”

“…Oxidative stress is implicated in the onset, progression and pathogenesis of numerous diseases and conditions, including periodontal disease, neurodegeneration and ageing [1][2][3][4][5][6][7][8]. Prolonged episodes of oxidative stress produces an excessive accumulation of reactive oxygen species (ROS), capable of inducing deleterious cellular and biomolecular damage to the host [1][2][3][4][5].…”

Neurological Disorders and Oxidative Toxic Stress: A Role of Metal Nanoparticles

“…Additionally, enhanced levels of OTS have been reported in the mice brain with apolipoprotein E deficiency exposed to concentrated ambient NPs (25). High prevalence of neurodegenerative diseases such as Alzheimer's disease and primary brain tumors has been reported, however, the exact etiology of them is not clear yet and OTS has been reported as a possible mechanism of such diseases (26)(27)(28)(29).…”

“…The high surface activity of NPs concentrated in the brain, during long-term exposures, may be related to cellular interactions and free radical formation leading to brain damage and increased risk of neurodegenerative conditions (25). Because of the high level of a metabolic rate, low endogenous scavenger levels, and extensive networks of neurons, the brain is more vulnerable to OTS than many other tissues (28). It has been reported that excessive accumulation of ROS resulted in irreversible neuronal death in the brain which may progress to develop neurodegenerative disorders (69).…”