Impact of Aging on Small Molecule Transport Across the Blood-Brain Barrier in Neurodegenerative Disorders

Neurodegenerative diseases (NDDs) such as Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD), Alzheimer’s Disease (AD), Parkinson’s Disease (PD), and Huntington Disease (HD) are projected to become the second leading cause of death by 2040, according to the World Health Organization (WHO). Despite the availability of conventional treatments like medications, therapies, and lifestyle adjustments, these interventions primarily manage symptoms rather than halt or reverse disease progression. Recent research has focused on developing therapies that can modify the underlying degenerative processes. A significant challenge in treating NDDs is the blood-brain barrier (BBB), a dynamic interface that protects the brain but also obstructs drug delivery. Traditional treatment options have largely been unsuccessful, with 190 investigational new drugs failing in clinical trials. The development of non-invasive drug delivery systems, particularly those involving small molecules, has shown promise due to their attributes such as easy oral administration, permeability, and target specificity. However, the BBB's tight junctions restrict the passage of many drugs, and the dynamics of drug transport can be further complicated by aging, which often leads to a decline in BBB integrity.

This research topic aims to investigate the impact of aging on small molecule transport across the blood-brain barrier in neurodegenerative disorders. The primary objectives include understanding the mechanisms behind altered small molecule transport due to aging, examining changes in ion channel and transporter dynamics, and exploring how these alterations contribute to the pathogenesis of neurodegeneration. Specific questions to be addressed include how aging affects BBB permeability, the role of efflux transporters and receptor molecules, and the implications of these changes for the development of targeted therapeutic strategies.

To gather further insights into the boundaries of this research, we welcome articles addressing, but not limited to, the following themes:

- Examination of transporter dynamics and receptor expression profiles in neurodegenerative disease models.
- Integration of in vivo imaging techniques to visualize BBB permeability and real-time small molecule transport.
- Examination of BBB disruption in AD and PD in small molecule drug therapeutic approaches.
- Study of BBB disruption associated with aging in neurological disorders.
- Examination of how iron transport dysfunction affects BBB integrity in neurological diseases.
- Study of how neuroinflammation impacts BBB dysfunction and integrity.
- Analysis of BBB permeability in Alzheimer’s disease.
- Investigation of neuroinflammation mechanisms in aging, particularly in relation to AD, and their therapeutic approaches.
- Examination of how activated microglial cells and astrocytes influence small molecule transport across BBB dysfunctions and their molecular mechanisms.

Keywords: Small Molecule Transport, Blood-Brain Barrier, Neuroinflammation, Neurodegenerative Disorders, Transporter Dynamics

Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.