Exploring the intersecting paths between metabolic disorders and neurological manifestations

Abstract

The metabolic derangements associated with inborn errors of metabolism, metabolic syndrome, and defective autophagy have been linked to neurological manifestations and an increased risk of developing certain neurological diseases or worsening their prognosis. Said metabolic derangements are primarily a consequence of genetic mutations that result in deficiencies of essential cellular components or the accumulation of toxic metabolites that negatively impact neuronal morphology and functionality. Additionally, blood-brain barrier dysfunction, increased quantity and damage of nonneuronal cells, diminished synaptic plasticity, and impediment of protein and neurotransmitter synthesis, among many others, are all neurological implications associated with various metabolic disarrangements. The past few decades have shown substantial efforts in linking various neurological pathologies to genetic variants of metabolic disorders. This review explores the implications of several inborn errors of metabolism, such as phenylketonuria, Wilson's disease, maple syrup urine disease, POLG-related diseases, and lysosomal storage diseases, and the implications of the components of metabolic syndrome in neuronal dysfunction and their link to neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and epilepsy. The correlation between defective autophagy, neurodegenerative diseases, and neurodevelopmental diseases is also explored at a molecular level. Congenital disorders of autophagy and their link to neurological pathologies are also discussed. Hence, these correlations provide insight into the underlying biological mechanism of metabolic diseases from a neurological standpoint. This review emphasizes the cruciality of understanding metabolic diseases as important variables in neurological health as well as isolated systemic problems.

Keywords Inherited errors of metabolism, Metabolic disorders, Neurological pathologies, Metabolic syndrome, Defective autophagy, Neurodegenerative diseases, Cognitive dysfunction