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CNS & Neurological Disorders - Drug Targets

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ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

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Review Article

Blood-brain Barrier and Neurovascular Unit Dysfunction in Parkinson's Disease: From Clinical Insights to Pathogenic Mechanisms and Novel Therapeutic Approaches

Author(s): Sarah Lei Qi Khor, Khuen Yen Ng, Rhun Yian Koh and Soi Moi Chye*

Volume 23, Issue 3, 2024

Published on: 05 May, 2023

Page: [315 - 330] Pages: 16

DOI: 10.2174/1871527322666230330093829

Price: $65

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.

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