Neurodegeneration refers to the gradual deterioration of neuron structure and
function and can lead to debilitating neurological conditions such as Alzheimer's
disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic
lateral sclerosis (ALS). Common pathogenic mechanisms on which many
neurodegenerative disorders (NDDs) are based include abnormal protein dynamics of
malfolding, degradation, proteasomal instability, and aggregation; often with molecular
chaperone actions and mutations; free radical/reactive oxygen species (ROS) formation
and OxS; bioenergetic weakness, mitochondrial dysfunction and damage to DNA,
neuronal Golgi system fragmentation, disruption of the movement of cellular/axonal,
neurotrophin (NTF) dysfunction and neuroinflammatory/neuroimmune processes.
Oxidative stress is a phenomenon caused by an imbalance between production and
accumulation of ROS/reactive nitrogen species (RNS) and/or a deficiency of enzymatic
and nonenzymatic antioxidants. Oxidative stress can be a result, but also an obesity
trigger. It has shown that obesity is coupled with an altered redox state and increased
metabolic risk. Antioxidant defenses in obese patients are decreased compared to the
control group, and their concentrations correlate inversely with core adiposity.
Moreover, obesity is also defined by increased concentrations of reactive oxygen or
nitrogen species. Metabolic changes caused by weight are associated with damage to
the central nervous system (CNS), which can result in neuronal death, either through
apoptosis or cell necrosis, or by modifying the neuron's synaptic plasticity. Adipose
tissue dysfunction associated with obesity has been correlated with abnormal brain
metabolism, neuroinflammation, brain atrophy, neural impairment, diminished mood,
and cognitive decline. Due to their high metabolic rate, visceral fat tissues function as
endocrine organs, which secrete adipokines (leptin, adiponectin, visfatin, resistin,
apelin, and plasminogen activator inhibitor type 1) and cytokines (TNF-α, IL-6, IL-1β).
Inflammatory cytokines bind to their receptors by activating the pathway of the nuclear
factor-kappaB, which induces a pro-inflammatory state. Inflammatory pathways and
DNA damage may also be triggered by nutritional imbalance, adversely affecting redox
control [via glutathione peroxidase (GPx); glutathione (GSH), and oxidized glutathione (GSSG) levels] and thus fostering oxidative stress. Obesity also impacts the glucose
and energy metabolism of brain cells, and by secreting pro-inflammatory agents causes
neuroinflammation primarily in the brain's hypothalamic area. The general effect is the
loss of neuronal activity and its internal molecular machinery, resulting in intracellular
or extracellular or both aberrant protein deposition, contributing to neurodegeneration.
Keywords: Adipokines, Cytokines, Metainflammation, Neuroinflammation,
Neurodegeneration, Neurodegenerative disease, Oxidative stress, Obesity.
