Metals are key players in maintaining and regulating gene expression,
antioxidant response, cell structure and neurotransmission. Their presence in the human
body is required in trace amounts to perform these functions, however, excessive
accumulation of these metals in various organs, including the brain, leads to
detrimental neurological consequences by altering oxidative stress, protein misfolding,
mitochondrial dysfunction, DNA fragmentation and apoptosis. These events over a
course of time contribute to mild cognitive impairment, movement related disorders,
learning and memory deficits which can further progress to neurodegeneration.
According to some epidemiological and clinical findings, there is strong evidence of
metal exposure and its correlation with a number of neurological diseases like
Alzheimer’s diseases (AD), Huntington’s disease (HD), amyotrophic lateral sclerosis
(ALS), Guillain-Barre disease (GBD), Parkinson’s disease (PD) and multiple sclerosis
(MS), etc. Moreover, metal ions tend to exacerbate the accumulation of neurotic
plaques in AD associated pathologies. It has been observed that metals like iron, zinc,
copper and Aluminium are elevated in AD brains, causing damage to the synapses.
Such metal ions imbalances are associated with aging related neuropathies and disease
progression. Some other factors contributing to neurodegeneration include
predisposition to ApoE allele, the interaction and synergistic effect of multiple metals
together, the impact of cholesterol, amyloid precursor protein (APP) processing, and
increased total tau along with Aβ production play a key role in increased biosynthesis
of reactive oxygen species in the brain. Such events tend to reduce neuronal viability
and function, thus causing cognitive decline.
Keywords: Metals, Mild cognitive Impairment, Neurodegeneration, Neurotoxi
city.
