Poly (ADP-Ribose) polymerase 1 and parthanatos in neurological diseases: From pathogenesis to therapeutic opportunities
Poly (ADP-ribose) polymerase-1 (PARP-1) is the most extensively studied member of the PARP superfamily, with its primary function being the facilitation of DNA damage repair processes. Parthanatos is a type of regulated cell death cascade initiated by PARP-1 hyperactivation, which involves multiple...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-10-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996123003303 |
| _version_ | 1827787405228244992 |
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| author | Xiaoxue Xu Bowen Sun Chuansheng Zhao |
| author_facet | Xiaoxue Xu Bowen Sun Chuansheng Zhao |
| author_sort | Xiaoxue Xu |
| collection | DOAJ |
| description | Poly (ADP-ribose) polymerase-1 (PARP-1) is the most extensively studied member of the PARP superfamily, with its primary function being the facilitation of DNA damage repair processes. Parthanatos is a type of regulated cell death cascade initiated by PARP-1 hyperactivation, which involves multiple subroutines, including the accumulation of ADP-ribose polymers (PAR), binding of PAR and apoptosis-inducing factor (AIF), release of AIF from the mitochondria, the translocation of the AIF/macrophage migration inhibitory factor (MIF) complex, and massive MIF-mediated DNA fragmentation. Over the past few decades, the role of PARP-1 in central nervous system health and disease has received increasing attention. In this review, we discuss the biological functions of PARP-1 in neural cell proliferation and differentiation, memory formation, brain ageing, and epigenetic regulation. We then elaborate on the involvement of PARP-1 and PARP-1-dependant parthanatos in various neuropathological processes, such as oxidative stress, neuroinflammation, mitochondrial dysfunction, excitotoxicity, autophagy damage, and endoplasmic reticulum (ER) stress. Additional highlight contains PARP-1's implications in the initiation, progression, and therapeutic opportunities for different neurological illnesses, including neurodegenerative diseases, stroke, autism spectrum disorder (ASD), multiple sclerosis (MS), epilepsy, and neuropathic pain (NP). Finally, emerging insights into the repurposing of PARP inhibitors for the management of neurological diseases are provided. This review aims to summarize the exciting advancements in the critical role of PARP-1 in neurological disorders, which may open new avenues for therapeutic options targeting PARP-1 or parthanatos. |
| first_indexed | 2024-03-11T16:48:48Z |
| format | Article |
| id | doaj.art-ffa482d1714f4167a04ce209f7e48ae3 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-03-11T16:48:48Z |
| publishDate | 2023-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-ffa482d1714f4167a04ce209f7e48ae32023-10-22T04:48:12ZengElsevierNeurobiology of Disease1095-953X2023-10-01187106314Poly (ADP-Ribose) polymerase 1 and parthanatos in neurological diseases: From pathogenesis to therapeutic opportunitiesXiaoxue Xu0Bowen Sun1Chuansheng Zhao2Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, China; Key Laboratory of Neurological Disease Big Data of Liaoning Province, Shenyang, China; Corresponding authors at: Department of Neurology, The First Hospital of China Medical University, No 155, Nanjing Street, Heping District, Shenyang, Liaoning 110001, China.Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, China; Key Laboratory of Neurological Disease Big Data of Liaoning Province, Shenyang, ChinaDepartment of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, China; Key Laboratory of Neurological Disease Big Data of Liaoning Province, Shenyang, China; Corresponding authors at: Department of Neurology, The First Hospital of China Medical University, No 155, Nanjing Street, Heping District, Shenyang, Liaoning 110001, China.Poly (ADP-ribose) polymerase-1 (PARP-1) is the most extensively studied member of the PARP superfamily, with its primary function being the facilitation of DNA damage repair processes. Parthanatos is a type of regulated cell death cascade initiated by PARP-1 hyperactivation, which involves multiple subroutines, including the accumulation of ADP-ribose polymers (PAR), binding of PAR and apoptosis-inducing factor (AIF), release of AIF from the mitochondria, the translocation of the AIF/macrophage migration inhibitory factor (MIF) complex, and massive MIF-mediated DNA fragmentation. Over the past few decades, the role of PARP-1 in central nervous system health and disease has received increasing attention. In this review, we discuss the biological functions of PARP-1 in neural cell proliferation and differentiation, memory formation, brain ageing, and epigenetic regulation. We then elaborate on the involvement of PARP-1 and PARP-1-dependant parthanatos in various neuropathological processes, such as oxidative stress, neuroinflammation, mitochondrial dysfunction, excitotoxicity, autophagy damage, and endoplasmic reticulum (ER) stress. Additional highlight contains PARP-1's implications in the initiation, progression, and therapeutic opportunities for different neurological illnesses, including neurodegenerative diseases, stroke, autism spectrum disorder (ASD), multiple sclerosis (MS), epilepsy, and neuropathic pain (NP). Finally, emerging insights into the repurposing of PARP inhibitors for the management of neurological diseases are provided. This review aims to summarize the exciting advancements in the critical role of PARP-1 in neurological disorders, which may open new avenues for therapeutic options targeting PARP-1 or parthanatos.http://www.sciencedirect.com/science/article/pii/S0969996123003303PARP-1parthanatosPARP-1 inhibitorsneuroinflammationoxidative stresscell death |
| spellingShingle | Xiaoxue Xu Bowen Sun Chuansheng Zhao Poly (ADP-Ribose) polymerase 1 and parthanatos in neurological diseases: From pathogenesis to therapeutic opportunities Neurobiology of Disease PARP-1 parthanatos PARP-1 inhibitors neuroinflammation oxidative stress cell death |
| title | Poly (ADP-Ribose) polymerase 1 and parthanatos in neurological diseases: From pathogenesis to therapeutic opportunities |
| title_full | Poly (ADP-Ribose) polymerase 1 and parthanatos in neurological diseases: From pathogenesis to therapeutic opportunities |
| title_fullStr | Poly (ADP-Ribose) polymerase 1 and parthanatos in neurological diseases: From pathogenesis to therapeutic opportunities |
| title_full_unstemmed | Poly (ADP-Ribose) polymerase 1 and parthanatos in neurological diseases: From pathogenesis to therapeutic opportunities |
| title_short | Poly (ADP-Ribose) polymerase 1 and parthanatos in neurological diseases: From pathogenesis to therapeutic opportunities |
| title_sort | poly adp ribose polymerase 1 and parthanatos in neurological diseases from pathogenesis to therapeutic opportunities |
| topic | PARP-1 parthanatos PARP-1 inhibitors neuroinflammation oxidative stress cell death |
| url | http://www.sciencedirect.com/science/article/pii/S0969996123003303 |
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