Besides extracellular deposition of amyloid beta and formation of phosphorylated tau in the brains of patients with Alzheimer's disease (AD), the pathogenesis of AD is also thought to involve mitochondrial dysfunctions and altered neurotransmission systems. However, none of these components can describe the diverse cognitive, behavioural, and psychiatric symptoms of AD without the pathologies interacting with one another. The purpose of this review is to understand the relationships between mitochondrial and neurotransmission dysfunctions in terms of (1) how mitochondrial alterations affect cholinergic and monoaminergic systems via disruption of energy metabolism, oxidative stress, and apoptosis; and (2) how different neurotransmission systems drive mitochondrial dysfunction via increasing amyloid beta internalisation, oxidative stress, disruption of mitochondrial permeabilisation, and mitochondrial trafficking. All these interactions are separately discussed in terms of neurotransmission systems. The association of mitochondrial dysfunctions with alterations in dopamine, norepinephrine, and histamine is the prospective goal in this research field. By unfolding the complex interactions surrounding mitochondrial dysfunction in AD, we can better develop potential treatments to delay, prevent, or cure this devastating disease.
Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by the hallmark pathologies of amyloid-beta plaques and neurofibrillary tangles. Symptoms of this devastating disease include behavioral changes and deterioration of higher cognitive functions. Impairment of neurogenesis has also been shown to occur in AD, which adversely impacts new neuronal cell growth, differentiation, and survival. This impairment possibly results from the cumulative effects of the various pathologies of AD. Preclinical studies have suggested that the administration of melatonin-the pineal hormone primarily responsible for the regulation of the circadian rhythm-targets the effects of AD pathologies and improves cognitive impairment. It is postulated that by mitigating the effect of these pathologies, melatonin can also rescue neurogenesis impairment. This review aims to explore the effect of AD pathologies on neurogenesis, as well as the mechanisms by which melatonin is able to ameliorate AD pathologies to potentially promote neurogenesis.
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