Article
Cell Biology
Zhengying Yu, Haipeng Wang, Wanyi Tang, Shaoyang Wang, Xiaoying Tian, Yujie Zhu, Hao He
Summary: A new optical method, UPLaS, has been developed to precisely and noninvasively induce localized mitochondrial Ca2+ oscillations, which directly initiates the PINK1-Parkin pathway for mitophagy.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Kanika Chandra, M. Swathi, B. Keerthana, Sooraj Gopan, Jyothi Priyanka Ghantasala, Manjunath B. Joshi, Manjunatha Thondamal, Kishore V. L. Parsa
Summary: Adaptability to intracellular or extracellular cues is crucial for maintaining cellular homeostasis. This study reveals the role of PHLPP1 in mitochondrial homeostasis, demonstrating its ability to regulate both fusion and fragmentation of mitochondria under different conditions.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Plant Sciences
Yanhong Cao, Xin Chen, Fuqiang Pan, Mingyang Wang, Haowen Zhuang, Jiangna Chen, Lu Lu, Lingjun Wang, Ting Wang
Summary: The Chinese herbal compound Xinmaikang (XMK) treats atherosclerosis (AS) by modulating macrophage mitophagy through the PINK1/Parkin signaling pathway. In vivo and in vitro experiments demonstrated that XMK reduces AS plaques, lipids, pro-inflammatory cytokines, and ROS levels, while promoting mitophagy. Knocking down PINK1 attenuated the effects of XMK on foam cell formation and PINK1/Parkin pathway activation.
Article
Pharmacology & Pharmacy
Shun Zhang, Yixin Wang, Yifan Cao, Jin Wu, Zubin Zhang, Haigang Ren, Xiaohui Xu, Elena Kaznacheyeva, Qing Li, Guanghui Wang
Summary: This study found that sorafenib and regorafenib induce cell death in hepatocellular carcinoma by damaging mitochondria, and mitophagy can alleviate this cell death. Inhibiting autophagy or mitochondrial fission can aggravate the cell death caused by these drugs. Additionally, knocking down the protein PINK1 can enhance the inhibitory effects of sorafenib and regorafenib on hepatocellular carcinoma.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Environmental Sciences
Bo Qian, Rong-Juan Jiang, Jia-Le Song, Chen-Qiang Wang
Summary: TDCPP-induced ferroptosis may be associated with its neurotoxicity, potentially through the PINK1/PARKIN-mediated mitophagy initiated by mitochondrial damage.
Article
Oncology
Yibin Zeng, Cui Xiong, Nan Tang, Siqi Wang, Zhiyong Xiong, Tao Liang, Qiangping Wang, Menglong Li, Junjun Li
Summary: There is growing evidence that aberrant expression of FAM72A contributes to mitochondrial dysfunction and has potential roles in various tumors, including glioma. This study identified FAM72A as a target molecule and found that it was significantly upregulated in glioma, correlated with WHO grade, and associated with poor clinical outcomes. Functional assays revealed that FAM72A promoted glioma cell growth through the Pink1/Parkin signaling pathway and also played a role in tumor immune escape by upregulating PD-L1 expression. Targeting FAM72A could be a promising therapeutic strategy for glioma.
Article
Cell Biology
Benjamin J. Broadway, Paige K. Boneski, Jenny M. Bredenberg, Ana Kolicheski, Xu Hou, Alexandra Soto-Beasley, Owen A. Ross, Wolfdieter Springer, Fabienne C. Fiesel
Summary: Loss of PINK1 or PRKN can cause early onset Parkinson's disease. Through analyzing a set of variants, this study identifies specific rare genetic PINK1 and PRKN variants that result in loss of enzymatic function and suggests their potential causative role in Parkinson's disease. Additionally, the study finds intermediate phenotypes in several variants and investigates the functional deficits of two variants using gene editing. The findings of this study contribute to the diagnostics and treatment of Parkinson's disease.
Article
Cell Biology
Waka Kojima, Koji Yamano, Hidetaka Kosako, Kenichiro Imai, Reika Kikuchi, Keiji Tanaka, Noriyuki Matsuda
Summary: Macroautophagy/autophagy is a complex intracellular degradation process with many regulatory factors. This study identified BCAS3 and C16orf70 as novel proteins associated with the autophagosome formation site and demonstrated their regulatory roles in autophagic activity. The BCAS3-C16orf70 complex affects the recruitment of core autophagy proteins to the phagophore assembly site.
Article
Pharmacology & Pharmacy
Sisi Lei, Yuchao Feng, Peiying Huang, BoJun Chen, Kun Bao, Qihua Wu, Haobo Zhang, Xiaoyan Huang
Summary: The study suggests that OPD'-induced cardiomyocyte mitophagy and mitochondrial damage are at least partially mediated by dysregulation of the PINK1/Parkin pathway.
Article
Cell Biology
Anbo Gao, Mengjie Wang, Xing Tang, Gangqing Shi, Kai Hou, Jinren Fang, Linlin Zhou, Hong Zhou, Weimin Jiang, Yukun Li, Fan Ouyang
Summary: Radiation-induced heart damage caused by low-dose X-rays leads to cardiac hypertrophy, and mitophagy activation plays a crucial role in this process.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Medicine, Research & Experimental
Lanqi Li, Tingjuan Huang, Jie Yang, Peidan Yang, Haixia Lan, Jian Liang, Donghong Cai, Huiya Zhong, Wei Jiao, Yafang Song
Summary: In this study, the mechanism by which AS-IV alleviates muscle injury by inhibiting excessive mitophagy through the PINK1/Parkin pathway was investigated. The results showed that AS-IV could reverse mitochondrial damage and excessive mitophagy, restoring the regulatory function of mitochondria.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Manxue Mei, Haoxiang Sun, Jiayu Xu, Yimeng Li, Guiling Chen, Qihua Yu, Changsheng Deng, Wei Zhu, Jianping Song
Summary: This study found that vanillic acid protected cardiomyocytes from oxidative stress injury by mediating mitophagy and improving mitochondrial function. The PINK1/Parkin/Mfn2 pathway may be involved in this protective mechanism. These findings have important implications for understanding the cardiovascular-protective effects of vanillic acid.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Reproductive Biology
Jiehuan Xu, Lingwei Sun, Caifeng Wu, Shushan Zhang, Shiqiang Ju, Rong Rui, Defu Zhang, Jianjun Dai
Summary: The study reveals that vitrification causes mitochondrial dysfunction and mitophagy in porcine oocytes, affecting embryonic developmental potential. Mitochondrial dysfunction under oxidative stress can be restored by antioxidant α-tocopherol, improving mitochondrial homeostasis and alleviating mitophagy.
Article
Clinical Neurology
Longfei Xing, Xilin Chen, Changqing Guo, Wenting Zhu, Tingyao Hu, Weiwei Ma, Mei Du, Yue Xu, Changqing Guo
Summary: The purpose of this study was to investigate whether mitophagy was involved in the cartilage protection of KOA rabbits after electroacupuncture intervention. It was found that electroacupuncture could reduce the degeneration of KOA cartilage and activate mitophagy in chondrocytes. This regulation might be achieved by upregulating the Pink1-Parkin signal pathway.
JOURNAL OF PAIN RESEARCH
(2023)
Article
Oncology
Jing Zhang, Sili Chen, Ye Li, Weichun Xiao, Wei An
Summary: Both lfALR and sfALR protect mitochondria by promoting PINK1/Parkin-dependent mitophagy through FOXO3a activation, indicating a novel mechanism for mitochondrial protection.
EXPERIMENTAL CELL RESEARCH
(2021)
Review
Cell Biology
Laura Smith, Anthony H. V. Schapira
Summary: Mutations in the GBA gene are the most important genetic risk factor for Parkinson's disease (PD), leading to protein metabolism abnormalities, lysosomal dysfunction, and lipid metabolism disorders. These mutations can trigger neurodegenerative processes through various mechanisms, including the accumulation of alpha-synuclein, endoplasmic reticulum stress responses, and mitochondrial dysfunction. Understanding these mechanisms can facilitate the development of targeted therapies for GBA-related PD.
Review
Clinical Neurology
Laura J. Smith, Chiao-Yin Lee, Elisa Menozzi, Anthony H. V. Schapira
Summary: Variants in the GBA1 and LRRK2 genes are common risk factors for Parkinson's disease. GBA1 is associated with lysosomal enzymes while LRRK2 affects the phosphorylation of GTPases. GBA1-related PD has earlier onset and more severe non-motor symptoms, while LRRK2-related PD has a milder disease course.
FRONTIERS IN NEUROLOGY
(2022)
Article
Gastroenterology & Hepatology
Marlene Schwarzfischer, Anna Niechcial, Kristina Handler, Yasser Morsy, Marcin Wawrzyniak, Andrea S. Laimbacher, Kirstin Atrott, Roberto Manzini, Katharina Baebler, Larissa Hering, Egle Katkeviciute, Janine Hafliger, Silvia Lang, Maja E. Keller, Jerome Woodtli, Lisa Eisenbeiss, Thomas Kraemer, Elisabeth M. Schraner, Mahesa Wiesendanger, Sebastian Zeissig, Gerhard Rogler, Andreas E. Moor, Michael Scharl, Marianne R. Spalinger
Summary: This study investigates the interaction between the PTPN22 gene variation and food-grade titanium dioxide nanoparticles in the pathogenesis of inflammatory bowel disease (IBD). The results show that the ingestion of titanium dioxide nanoparticles makes mice carrying the PTPN22 variation susceptible to IBD and triggers severe intestinal inflammation. This demonstrates that environmental factors can interact with genetic risk variants and reverse a protective mechanism into a disease-promoting effect.
Article
Biochemistry & Molecular Biology
Laura J. Smith, Magdalena M. Bolsinger, Kai-Yin Chau, Matthew E. Gegg, Anthony H. Schapira
Summary: Sequence variants or mutations in the GBA gene are the most important risk factor for Parkinson's disease. This study characterizes the effects of the E326K variant in human cells and finds that it behaves differently compared to other common GBA mutations. However, lipid imbalance and alpha-synuclein pathology are still observed.
HUMAN MOLECULAR GENETICS
(2023)
Article
Gastroenterology & Hepatology
Joana Torres, Maria Chaparro, Mette Julsgaard, Konstantinos Katsanos, Zuzana Zelinkova, Manasi Agrawal, Sandro Ardizzone, Marjo Campmans-Kuijpers, Gabriele Dragoni, Marc Ferrante, Gionata Fiorino, Emma Flanagan, Catarina Frias Gomes, Ailsa Hart, Charlotte Rose Hedin, Pascal Juillerat, Annemarie Mulders, Par Myrelid, Aoibhlinn O'Toole, Pauline Riviere, Michael Scharl, Christian Philipp Selinger, Elena Sonnenberg, Murat Toruner, Jantien Wieringa, C. Janneke Van der Woude
JOURNAL OF CROHNS & COLITIS
(2023)
Article
Biochemistry & Molecular Biology
Adam R. R. Smith, David M. M. Richards, Katie Lunnon, Anthony H. V. Schapira, Anna Migdalska-Richards
Summary: Parkinson's disease (PD) is a common movement disorder, and mutations in the GBA1 gene are the most common genetic risk factor for PD. PD-GBA1 is distinct from idiopathic PD in terms of age of onset, neuropsychiatric symptoms, and cognitive impairment. This study found differences in DNA methylation levels of the SNCA gene between PD-GBA1 and idiopathic PD, suggesting the existence of different genetic subtypes within PD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Electra Brunialti, Alessandro Villa, Marco Toffoli, Sara Lucas Del Pozo, Nicoletta Rizzi, Clara Meda, Adriana Maggi, Anthony H. V. Schapira, Paolo Ciana
Summary: Microglia are heterogenous cells in the nervous system that have distinct populations contributing to specific processes, including neuroprotection. Our study found that male microglia tend to have a more pro-inflammatory phenotype, while female microglia are more sensitive to glucocerebrosidase inhibition. Furthermore, glucocerebrosidase inhibition impaired the ability of female microglia to enhance the Nrf2-dependent detoxification pathway in neurons.
Article
Clinical Neurology
Tom Foltynie, Sonia Gandhi, Cristina Gonzalez-Robles, Marie-Louise Zeissler, Georgia Mills, Roger Barker, James Carpenter, Anette Schrag, Anthony Schapira, Oliver Bandmann, Stephen Mullin, Joy Duffen, Kevin McFarthing, Jeremy Chataway, Mahesh Parmar, Camille Carroll
Summary: Multi-arm, multi-stage platform designs have improved the efficiency of clinical trials in the field of oncology. Foltynie et al. discuss the challenges and considerations of using this approach to assess potential disease-modifying treatments in progressive neurological conditions such as Parkinson's disease.
Article
Clinical Neurology
Cornelis Blauwendraat, Nahid Tayebi, Elizabeth Geena Woo, Grisel Lopez, Luca Fierro, Marco Toffoli, Naomi Limbachiya, Derralynn Hughes, Vanessa Pitz, Dhairya Patel, Dan Vitale, Mathew J. Koretsky, Dena Hernandez, Raquel Real, Roy N. Alcalay, Mike A. Nalls, Huw R. Morris, Anthony H. V. Schapira, Manisha Balwani, Ellen Sidransky
Summary: This study found that PD patients with GD1 have a higher genetic risk score, suggesting that common risk variants may affect underlying biological pathways.
MOVEMENT DISORDERS
(2023)
Letter
Clinical Neurology
Marco Toffoli, Anthony H. V. Schapira, Christos Proukakis
MOVEMENT DISORDERS
(2023)
Article
Clinical Neurology
Siegfried Karl Wagner, David Romero-Bascones, Mario Cortina-Borja, Dominic J. Williamson, Robbert R. Struyven, Yukun Zhou, Salil Patel, Rimona S. Weil, Chrystalina A. Antoniades, Eric J. Topol, Edward Korot, Paul J. Foster, Konstantinos Balaskas, Unai Ayala, Maitane Barrenechea, Inigo Gabilondo, Anthony H. V. Schapira, Anthony P. Khawaja, Praveen J. Patel, Jugnoo S. Rahi, Alastair K. Denniston, Axel Petzold, Pearse Andrew Keane
Summary: Individuals with Parkinson's disease (PD) exhibit reduced thickness of the inner nuclear layer (INL) and ganglion cell-inner plexiform layer (GCIPL) of the retina. Changes in these layers occurring several years before clinical presentation highlight a potential role for retinal imaging in stratifying PD risk.
Article
Environmental Studies
Aaron Bradshaw
Summary: This article examines how digital technologies are used to sense and encounter overlooked microbial ecologies in a polluted urban river in East London, revealing the intersection of urban political ecological, hydrological, and microbiological dynamics.
CULTURAL GEOGRAPHIES
(2023)
Article
Clinical Neurology
Cornelis Blauwendraat, Nahid Tayebi, Elizabeth Geena Woo, Grisel Lopez, Luca Fierro, Marco Toffoli, Naomi Limbachiya, Derralynn Hughes, Vanessa Pitz, Dhairya Patel, Dan Vitale, Mathew J. Koretsky, Dena Hernandez, Raquel Real, Roy N. Alcalay, Mike A. Nalls, Huw R. Morris, Anthony H. V. Schapira, Manisha Balwani, Ellen Sidransky
Summary: This study investigated the contribution of PD risk variants to risk for PD in patients with GD1. The results showed that patients with GD1 who developed PD had a significantly higher PD genetic risk score than those without PD. This suggests that common risk variants may affect underlying biological pathways.
MOVEMENT DISORDERS
(2023)
Meeting Abstract
Clinical Neurology
C. Gonzalez-Robles, D. Byrom, R. Chapman, D. Dexter, S. Duty, R. Ellis-Doyle, E. Jabbari, G. Mills, H. Mortiboys, J. Rudiger, E. Sammler, P. Scurfield, S. Stott, G. Tofaris, L. Wei, A. Wong, M. L. Zeissler, C. Carroll, T. Foltynie, O. Bandmann, A. Schapira
MOVEMENT DISORDERS
(2022)
Meeting Abstract
Clinical Neurology
L. Smith, M. Gegg, D. Chau, A. H. V. Schapira
MOVEMENT DISORDERS
(2022)