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Alzheimers disease (AD) is one of the most common neurodegenerative diseases in existence. It is characterized by an impaired cognitive function that is due to a progressive loss of neurons in the brain. Extracellular -amyloid (A) plaques are the main pathological features of the disease. In addition to abnormal protein aggregation, increased mitochondrial fragmentation, altered expression of the genes involved in mitochondrial biogenesis, disruptions in the ERmitochondria interaction, and mitophagy are observed. Reactive oxygen species are known to affect A expression and aggregation. In turn, oligomeric and aggregated A cause mitochondrial disorders. In this review, we summarize available knowledge about the pathological effects of A on mitochondria and the potential molecular targets associated with proteinopathy and mitochondrial dysfunction for the pharmacological treatment of Alzheimers disease.

Drug development for the treatment of neurodegenerative diseases has to confront numerous problems occurring, in particular, because of attempts to address only one of the causes of the pathogenesis of neurological disorders. Recent advances in multitarget therapy research are gaining momentum by utilizing pharmacophores that simultaneously affect different pathological pathways in the neurodegeneration process. The application of such a therapeutic strategy not only involves the treatment of symptoms, but also mainly addresses prevention of the fundamental pathological processes of neurodegenerative diseases and the reduction of cognitive abilities. Neuroinflammation and oxidative stress, mitochondrial dysfunction, dysregulation of the expression of histone deacetylases, and aggregation of pathogenic forms of proteins are among the most common and significant pathological features of neurodegenerative diseases. In this review, we focus on the molecular mechanisms and highlight the main aspects, including reactive oxygen species, the cell endogenous antioxidant system, neuroinflammation triggers, metalloproteinases, -synuclein, tau proteins, neuromelanin, histone deacetylases, presenilins, etc. The processes and molecular targets discussed in this review could serve as a starting point for screening leader compounds that could help prevent or slow down the development of neurodegenerative diseases.