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<p>Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by bradykinesia, tremor, rigidity, and postural instability resulting from the selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The pathology of PD is complex and multifactorial, involving mitochondrial dysfunction, oxidative stress, impaired protein clearance, neuroinflammation, and impaired blood–brain barrier (BBB) integrity. Genetic mutations, including those in the alpha-synuclein (SNCA), PTEN-induced kinase 1 (PINK1), and leucine-rich repeat kinase 2 (LRRK2) genes, as well as environmental factors such as pesticides and neurotoxins, have also been implicated in the onset and progression of PD. ATP-binding cassette sub-family B member 1 (ABCB1), an ATP-dependent efflux protein transporter located at the luminal surface of the BBB, is known to play a crucial role in protecting the brain from neurotoxic agents, misfolded proteins, and xenobiotics. Recent studies have shown that ABCB1 dysfunction in PD can compromise the integrity of the BBB, impair the clearance of misfolded proteins, xenobiotics, and environmental toxins, and increase neuroinflammation, mitochondrial dysfunction, and oxidative stress and thereby exacerbate dopaminergic neurodegeneration. Additionally, ABCB1 modulates the pharmacokinetics of several antiparkinsonism drugs, including levodopa, potentially limiting their efficacy by restricting CNS penetration. Moreover, alteration in ABCB1 function, influenced by genetic polymorphisms and inflammatory cytokines, may contribute to disease progression and drug resistance. This review highlights the multifaceted role of ABCB1 in PD pathogenesis and explores its potential as a therapeutic target. Modulating ABCB1 activity may offer promising strategies to enhance drug delivery, reduce neurotoxicity, and slow disease progression, thereby improving clinical outcomes for PD patients.</p>

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Gatekeeper of the brain: unraveling the role of ABCB1 in Parkinson’s disease progression and therapy

  • 期刊论文

  • 发表日期：

    2025年9月6日

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  • Bhat Zada Unjum Saqib,
  • Royal Patel,
  • Pratyush Porel,
  • Khadga Raj Aran

摘要

Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by bradykinesia, tremor, rigidity, and postural instability resulting from the selective loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The pathology of PD is complex and multifactorial, involving mitochondrial dysfunction, oxidative stress, impaired protein clearance, neuroinflammation, and impaired blood–brain barrier (BBB) integrity. Genetic mutations, including those in the alpha-synuclein (SNCA), PTEN-induced kinase 1 (PINK1), and leucine-rich repeat kinase 2 (LRRK2) genes, as well as environmental factors such as pesticides and neurotoxins, have also been implicated in the onset and progression of PD. ATP-binding cassette sub-family B member 1 (ABCB1), an ATP-dependent efflux protein transporter located at the luminal surface of the BBB, is known to play a crucial role in protecting the brain from neurotoxic agents, misfolded proteins, and xenobiotics. Recent studies have shown that ABCB1 dysfunction in PD can compromise the integrity of the BBB, impair the clearance of misfolded proteins, xenobiotics, and environmental toxins, and increase neuroinflammation, mitochondrial dysfunction, and oxidative stress and thereby exacerbate dopaminergic neurodegeneration. Additionally, ABCB1 modulates the pharmacokinetics of several antiparkinsonism drugs, including levodopa, potentially limiting their efficacy by restricting CNS penetration. Moreover, alteration in ABCB1 function, influenced by genetic polymorphisms and inflammatory cytokines, may contribute to disease progression and drug resistance. This review highlights the multifaceted role of ABCB1 in PD pathogenesis and explores its potential as a therapeutic target. Modulating ABCB1 activity may offer promising strategies to enhance drug delivery, reduce neurotoxicity, and slow disease progression, thereby improving clinical outcomes for PD patients.