The Crucial Role of the Blood–Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications

Abstract

The blood–brain barrier (BBB) is a crucial structure that maintains brain homeostasis by regulating the entry of molecules and cells from the bloodstream into the central nervous system (CNS). Neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease, as well as ischemic stroke, compromise the integrity of the BBB. This leads to increased permeability and the infiltration of harmful substances, thereby accelerating neurodegeneration. In this review, we explore the mechanisms underlying BBB disruption, including oxidative stress, neuroinflammation, vascular dysfunction, and the loss of tight junction integrity, in patients with neurodegenerative diseases. We discuss how BBB breakdown contributes to neuroinflammation, neurotoxicity, and the abnormal accumulation of pathological proteins, all of which exacerbate neuronal damage and facilitate disease progression. Furthermore, we discuss potential therapeutic strategies aimed at preserving or restoring BBB function, such as anti-inflammatory treatments, antioxidant therapies, and approaches to enhance tight junction integrity. Given the central role of the BBB in neurodegeneration, maintaining its integrity represents a promising therapeutic approach to slow or prevent the progression of neurodegenerative diseases.