Title:Blood-brain Barrier and Neurovascular Unit Dysfunction in Parkinson's Disease: From Clinical Insights to Pathogenic Mechanisms and Novel
Therapeutic Approaches
Volume: 23
Issue: 3
Author(s): Sarah Lei Qi Khor, Khuen Yen Ng, Rhun Yian Koh and Soi Moi Chye*
Affiliation:
- Division of Applied Biomedical Science and Biotechnology, School of
Health Science, International Medical University, 57000, Kuala Lumpur, Malaysia
Keywords:
Parkinson’s disease, blood-brain barrier, neurovascular unit, pathogenesis, neuroendocrine regulation, therapeutic interventions.
Abstract: The blood-brain barrier (BBB) plays a crucial role in the central nervous system by tightly
regulating the influx and efflux of biological substances between the brain parenchyma and peripheral
circulation. Its restrictive nature acts as an obstacle to protect the brain from potentially noxious substances
such as blood-borne toxins, immune cells, and pathogens. Thus, the maintenance of its structural
and functional integrity is vital in the preservation of neuronal function and cellular homeostasis
in the brain microenvironment. However, the barrier’s foundation can become compromised during
neurological or pathological conditions, which can result in dysregulated ionic homeostasis, impaired
transport of nutrients, and accumulation of neurotoxins that eventually lead to irreversible neuronal
loss. Initially, the BBB is thought to remain intact during neurodegenerative diseases, but accumulating
evidence as of late has suggested the possible association of BBB dysfunction with Parkinson’s
disease (PD) pathology. The neurodegeneration occurring in PD is believed to stem from a myriad of
pathogenic mechanisms, including tight junction alterations, abnormal angiogenesis, and dysfunctional
BBB transporter mechanism, which ultimately causes altered BBB permeability. In this review, the
major elements of the neurovascular unit (NVU) comprising the BBB are discussed, along with their
role in the maintenance of barrier integrity and PD pathogenesis. We also elaborated on how the neuroendocrine
system can influence the regulation of BBB function and PD pathogenesis. Several novel
therapeutic approaches targeting the NVU components are explored to provide a fresh outlook on
treatment options for PD.