Neurochemical and neuroimaging α-Synuclein dynamics in cellular and molecular mechanisms of brain aging

α-Synuclein is a protein predominantly associated with neurodegenerative disorders, where its accumulation and aggregation are critical markers of disease progression. In the context of brain aging, α-synuclein plays a complex role, influencing various cellular pathways and potentially exacerbating the effects of aging at a molecular level. Research into how α-synuclein dynamics alter with age and contribute to neurodegenerative processes is essential for developing strategies to prevent or slow these conditions. This understanding is increasingly vital as global demographics shift towards an older population more susceptible to neurodegenerative diseases. In vivo functional and structural brain imaging of synucleinopathies in humans have provided a rich new understanding of the affected networks across the cortex and subcortex. Despite this progress, the temporal relationship between α-synuclein (α-syn) pathology and the functional and structural changes occurring in the brain is not well understood.

The protein α-synuclein plays a crucial role in the pathology of several neurodegenerative diseases, prominently Parkinson’s, other synucleinopathies and Alzheimer’s. Its misfolding and aggregation are believed to contribute significantly to the neuronal dysfunction and death characteristic of these diseases. However, the specific mechanisms through which α-synuclein impacts brain aging remain unclear. This Research Topic seeks to elucidate the role of α-synuclein in the aging brain, aiming to uncover the cellular and molecular pathways affected by its dynamics. By fostering a deeper understanding of these processes, we aim to identify potential therapeutic targets that could mitigate the effects of brain aging and related diseases.

This Research Topic aims to explore several facets of α-synuclein dynamics within the aging brain:

-The role of α-synuclein in neuronal senescence and its impact on neuron survival and functionality.

-Interactions between α-synuclein and other aging biomarkers and the resulting implications for brain health.

-The influence of genetic variants on α-synuclein expression and its pathological consequences.

-Novel therapeutic targets within the α-synuclein pathways for treating aging-related neurodegeneration.

-Technological advancements in studying α-synuclein, including new methodologies for tracking its dynamics in the aging brain.

Over the past five years, a-synuclein seeding assays (SAAs) have emerged as promising biomarkers for PD and other synucleinopathies, resulting in a shift in the conceptual framework of PD. We invite original research articles, comprehensive review papers, and brief reports that contribute to these themes. Contributions from neuroscientists, molecular biologists, geneticists, and clinicians are especially welcome, as are multidisciplinary approaches that combine insights from biochemistry, gerontology, and neuropharmacology.