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

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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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:23

Enthalten in:

CNS & neurological disorders drug targets - 23(2024), 3 vom: 18., Seite 315-330

Sprache:

Englisch

Beteiligte Personen:

Khor, Sarah Lei Qi [VerfasserIn]
Ng, Khuen Yen [VerfasserIn]
Koh, Rhun Yian [VerfasserIn]
Chye, Soi Moi [VerfasserIn]

Links:

Volltext

Themen:

Blood-brain barrier
Journal Article
Neuroendocrine regulation
Neurovascular unit
Parkinson’s disease
Pathogenesis
Research Support, Non-U.S. Gov't
Review
Therapeutic interventions.

Anmerkungen:

Date Completed 11.01.2024

Date Revised 19.04.2024

published: Print

Citation Status MEDLINE

doi:

10.2174/1871527322666230330093829

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM355040921