Abstract
Alzheimer’s disease (AD) represents the principal cause of dementia among the elderly. Great efforts have been established to understand the physiopathology of AD. Changes in neurotransmitter systems in patients with AD, including cholinergic, GABAergic, serotoninergic, noradrenergic, and histaminergic changes have been reported. Interestingly, changes in the histaminergic system have been related to cognitive impairment in AD patients. The principal pathological changes in the brains of AD patients, related to the histaminergic system, are neurofibrillary degeneration of the tuberomammillary nucleus, the main source of histamine in the brain, low histamine levels, and altered signaling of its receptors. The increase of histamine levels can be achieved by inhibiting its degrading enzyme, histamine N-methyltransferase (HNMT), a cytoplasmatic enzyme located in astrocytes. Thus, increasing histamine levels could be employed in AD patients as co-therapy due to their effects on cognitive functions, neuroplasticity, neuronal survival, neurogenesis, and the degradation of amyloid beta (Aβ) peptides. In this sense, the evaluation of the impact of HNMT inhibitors on animal models of AD would be interesting, consequently highlighting its relevance.
Highlights
Nowadays, Alzheimer’s disease (AD) represents a disorder with no permanent cure.The main clinical manifestations are related to learning and memory disabilities and other cognitive symptoms that impair independence and quality of life [1]
The study of AD has been focused on two principal histopathological hallmarks: amyloid β (Aβ) plaque deposits and intracellular neurofibrillary tangles (NFTs) in the brain [3]
The principal neurotransmitter systems altered in patients with AD are cholinergic and glutamatergic systems, which are especially affected by neurodegeneration, which in turn, allowed for the development of acetylcholinesterase (AChE) inhibitors and antagonists of N-methyl-D-aspartate (NMDA) receptors, the main drugs employed to treat AD [5]
Summary
Alzheimer’s disease (AD) represents a disorder with no permanent cure. The main clinical manifestations are related to learning and memory disabilities and other cognitive symptoms that impair independence and quality of life [1]. Brain histaminergic system results are of particular interest as a potential target to modify the cognitive symptoms of AD [8] In this sense, enhancing histaminergic neurotransmission in AD patients could result in beneficial effects such as improvement of Biomolecules 2021, 11, x FOR PEER REVIEW cognitive symptoms and neuroplasticity [9] increase in the degradation of extracellular Aβ insoluble plaques [10], lowering Aβ pathology [11] and increase neurogenesis [12]. In this sense, it has been demonstrated that the regulation of histamine concentration. Reactive oxygen species enhance Aβ levels and accumulate, resulting in the potentiation of neuronal damage [28]
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