Alzheimer's disease (AD), the most prevalent
neurodegenerative disease worldwide, has two main hallmarks: extracellular deposits of
amyloid β-
peptide (Aβ) and intracellular neurofibrillary tangles composed by
tau protein. Most AD cases are sporadic and are not dependent on known genetic causes; aging is the major risk factor for AD. Therefore, the oxidative stress has been proposed to initiate the uncontrolled increase in Aβ production and also to mediate the Aβ's deleterious effects on brain cells, especially on neurons from the cortex and hippocampus. The production of
free radicals in the presence of
nitric oxide (NO) yields to the
peroxynitrite generation, a very reactive agent that nitrotyrosinates the
proteins irreversibly. The nitrotyrosination produces a loss of
protein physiological functions, contributing to accelerate AD progression. One of the most nitrotyrosinated
proteins in AD is the
enzyme triosephosphate isomerase (TPI) that isomerises
trioses, regulating
glucose consumption by both
phosphate pentose and glycolytic pathways and thereby
pyruvate production. Hence, any disturbance in the
glucose supply could affect the proper brain function, considering that the brain has a high rate of
glucose consumption. Besides this directly affecting to the energetic metabolism of the neurons, TPI modifications, such as mutation or nitrotyrosination, increase
methylglyoxal production, a toxic precursor of advanced glycated end-products (AGEs) and responsible for protein glycation. Moreover, nitro-TPI aggregates interact with
tau protein inducing the intraneuronal aggregation of tau. Here we review the relationship between modified TPI and AD, highlighting the relevance of this
protein in AD pathology and the consequences of
protein nitro-oxidative modifications.