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Investigations of brain aging have continuously progressed over the past several decades. Since an increase in age is the greatest risk factor for dementia and related disorders, much attention has been focused on research to understand the mechanisms of disease-related brain aging. Neurodegenerative diseases ...

Investigations of brain aging have continuously progressed over the past several decades. Since an increase in age is the greatest risk factor for dementia and related disorders, much attention has been focused on research to understand the mechanisms of disease-related brain aging. Neurodegenerative diseases including Alzheimer’s disease, dementia with Lewy bodies, and frontotemporal lobar degeneration are mostly diagnosed by neuropathological features with protein inclusions such as Aβ, tau, α-synuclein, TDP-43, and FUS. These proteins are expected to lose physiological function and interact with functional molecules with age. Consequently, acquired pathologies of aged proteins are accumulated and propagated in neural cells.

To prove these theories, a research initiative, “brain protein aging and dementia control” has been established in a Japanese research consortium. We (Dr. Sobue and his colleagues) created the neologism of “Brain protein aging," which could be controlled and facilitated by various factors such as degradation, excretory mechanisms, stress, inflammation, genetic factors. The study of “brain protein aging” also includes the investigation of mechanisms of age-related neurodegeneration at the protein level. At this moment, the process of brain aging, the expression of neural toxicity and the mechanism of neural circuit breakdown are not entirely clear. Therefore, our research initiative sets goals to clarify the mechanisms of initiation and pathologies of aging, to clarify the mechanisms of intercellular transmission and ineffectiveness of toxic proteins, and to develop biomarkers and drugs for neurological disease.

We still don’t know why brain aging exists or how the brain is aging. Therefore, this Research Topic aims to propose an innovative area in the research field of age-related neurological diseases. As the first step towards creating this research area, the latest progress in our understanding of “Brain protein aging” will be presented.

Keywords: aging, neurodegeneration, protein


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