Mitochondrial permeability transition (mPT) is a critical process in neurodegenerative diseases, leading to cell death and neuronal loss. This review explores the role of mPT in neurodegenerative disorders, focusing on its induction by factors such as free radicals and calcium. The mPTP, a pore in the mitochondrial membrane, is involved in the initial steps of apoptosis and necrosis, contributing to the irreversible loss of neurons. Despite evidence linking mPTP to neurodegeneration, the exact mechanisms and structure of the pore remain debated. The study highlights the challenges in developing neuroprotective strategies targeting mPTP, including the difficulty in detecting mPT in live cells and the need for more specific inhibitors. The review covers major neurodegenerative diseases, including Alzheimer's, Parkinson's, ALS, frontotemporal dementia, and Huntington's disease, discussing how mPTP contributes to their pathogenesis. For example, in Alzheimer's, aggregated β-amyloid induces mPTP opening, leading to mitochondrial dysfunction and cell death. In Parkinson's, mitochondrial toxins and protein misfolding contribute to mPTP activation. The review also discusses the potential of mPTP inhibitors, such as cyclosporine A, in neuroprotection, despite their limitations in clinical use due to toxicity. The study emphasizes the importance of understanding mPTP in developing effective therapies for neurodegenerative diseases.Mitochondrial permeability transition (mPT) is a critical process in neurodegenerative diseases, leading to cell death and neuronal loss. This review explores the role of mPT in neurodegenerative disorders, focusing on its induction by factors such as free radicals and calcium. The mPTP, a pore in the mitochondrial membrane, is involved in the initial steps of apoptosis and necrosis, contributing to the irreversible loss of neurons. Despite evidence linking mPTP to neurodegeneration, the exact mechanisms and structure of the pore remain debated. The study highlights the challenges in developing neuroprotective strategies targeting mPTP, including the difficulty in detecting mPT in live cells and the need for more specific inhibitors. The review covers major neurodegenerative diseases, including Alzheimer's, Parkinson's, ALS, frontotemporal dementia, and Huntington's disease, discussing how mPTP contributes to their pathogenesis. For example, in Alzheimer's, aggregated β-amyloid induces mPTP opening, leading to mitochondrial dysfunction and cell death. In Parkinson's, mitochondrial toxins and protein misfolding contribute to mPTP activation. The review also discusses the potential of mPTP inhibitors, such as cyclosporine A, in neuroprotection, despite their limitations in clinical use due to toxicity. The study emphasizes the importance of understanding mPTP in developing effective therapies for neurodegenerative diseases.