Article
Cell Biology
Takeshi Yamamoto, Yoshitsugu Takabatake, Satoshi Minami, Shinsuke Sakai, Ryuta Fujimura, Atsushi Takahashi, Tomoko Namba-Hamano, Jun Matsuda, Tomonori Kimura, Isao Matsui, Jun-Ya Kaimori, Hiroaki Takeda, Masatomo Takahashi, Yoshihiro Izumi, Takeshi Bamba, Taiji Matsusaka, Fumio Niimura, Motoko Yanagita, Yoshitaka Isaka
Summary: The study found that supplementation with EPA can alleviate renal lipotoxicity by reducing phospholipid accumulation in lysosomes, improving mitochondrial dysfunction, reducing inflammation and fibrosis. EPA alleviates renal lipotoxicity by improving lysosomal function and autophagic flux in both high-fat diet-fed mice and isolated PTECs cultured in palmitic acid, indicating its potential as a novel treatment for obesity-related kidney diseases.
Review
Genetics & Heredity
Eun-Mi Hur, Byoung Dae Lee
Summary: Parkinson's disease is a heterogeneous neurodegenerative disease characterized by the loss of dopaminergic neurons and the formation of proteinaceous inclusions. Aging is considered a major risk factor influencing the progression of PD, with common changes in cellular functions shared by aging and PD. Mutations in the LRRK2 gene are a common genetic cause of both familial and sporadic PD, and may interact with aging to contribute to PD pathologies.
Review
Neurosciences
Fan Zhang, Zhiwei Wu, Fei Long, Jieqiong Tan, Ni Gong, Xiaorong Li, Changwei Lin
Summary: This article summarizes the effects of ATP13A2 gene mutations on PD, discusses the molecular mechanism of lysosomal autophagy inhibition and abnormal alpha-synuclein accumulation, and provides a new direction for future research on the pathogenesis and therapeutic targets of ATP13A2 gene-related PD.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Review
Cell Biology
Remi Kinet, Benjamin Dehay
Summary: The aging population and lack of curative treatment for Parkinson's disease pose essential challenges in the coming years, making research crucial for therapeutic developments. Advances in understanding this neurodegenerative disorder have led to the discovery of new pathogenesis-related genes through genome-wide association analysis. Additionally, recent insights into the connection between Parkinson's disease and disrupted autophagy mechanisms have allowed the development of animal models mimicking autophagic dysregulation, providing opportunities to explore potential therapeutic strategies for restoring autophagy activity.
Article
Biochemistry & Molecular Biology
Melissa Vos, Christine Klein, Andrew A. Hicks
Summary: Sphingolipids, a subset of bioactive lipids, play a crucial role in proper neuronal function and are involved in almost all biological processes. Recent studies have found alterations in sphingolipids in patients with Parkinson's disease (PD), suggesting an important interaction between sphingolipids and PD-related cellular processes. This article discusses the role of sphingolipids in mitochondrial dysfunction, autophagy defects, and abnormal endosomal activity in PD.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Review
Neurosciences
Martin Lang, Peter P. Pramstaller, Irene Pichler
Summary: Living organisms need to adapt and handle stress, and mitochondria and lysosomes play a key role in regulating energy and nutrient availability within cells. Dysfunction in these mechanisms can lead to pathologies, such as Parkinson's disease. Mitochondrial dysfunction and defects in the autophagy-lysosomal pathway have been observed in PD patients and models, and the MiT pathway, which regulates cellular homeostasis, could be a potential therapeutic target against PD.
MOLECULAR NEURODEGENERATION
(2022)
Review
Cell Biology
Eddie Pradas, Marta Martinez-Vicente
Summary: GBA gene variants are the first genetic risk factor for Parkinson's disease. GBA encodes the lysosomal enzyme glucocerebrosidase (GBA), which is involved in sphingolipid metabolism. The loss of GBA activity has been associated with the accumulation of alpha-synuclein species.
Article
Pharmacology & Pharmacy
Angelica Jardim Costa, Adolfo Garcia Erustes, Rita Sinigaglia, Carlos Eduardo Neves Girardi, Gustavo Jose da Silva Pereira, Rodrigo Portes Ureshino, Soraya Soubhi Smaili
Summary: In young striatum, lithium increased tissue viability and decreased ROS generation, accompanied by enhanced expression of autophagy-related proteins. However, in aged striatum, lithium reduced autophagic flux and increased oxygen consumption rate. Ultrastructural changes in aged rats' striatum included electron-dense mitochondria with disarranged cristae after consuming lithium for 30 days.
Article
Cell Biology
Satoshi Minami, Shinsuke Sakai, Takeshi Yamamoto, Yoshitsugu Takabatake, Tomoko Namba-Hamano, Atsushi Takahashi, Jun Matsuda, Hiroaki Yonishi, Jun Nakamura, Shihomi Maeda, Sho Matsui, Isao Matsui, Yoshitaka Isaka
Summary: Chronic kidney disease (CKD) has become an epidemic worldwide due to aging and increased obesity. The study reveals that autophagy deficiency induces the expression of FGF21, which plays a protective role against CKD progression by improving autophagy stagnation and maintaining mitochondrial homeostasis. This finding provides a potential novel treatment for CKD.
Review
Cell Biology
Manuela Morleo, Helena L. A. Vieira, Petra Pennekamp, Alessandro Palma, Liliana Bento-Lopes, Heymut Omran, Susana S. Lopes, Duarte C. Barral, Brunella Franco
Summary: Macroautophagy/autophagy is a self-degradative process that helps cells maintain energy balance. It has been found to have an interplay with cilia, microtubule-based organelles on mammalian cells. The selective autophagic degradation of ciliary proteins controls ciliogenesis, and cilia also control autophagy. The molecular mechanisms underlying this interaction are still not fully understood, and conflicting data exist. Understanding this axis is important for ciliopathies and autophagy-associated disorders.
Review
Biochemistry & Molecular Biology
Michael Takla, Swati Keshri, David C. Rubinsztein
Summary: TFEB is a critical transcription factor involved in multiple physiological functions. Pathological states modify TFEB function by regulating its post-translational modifications, which can have both protective and deleterious effects on tissue survival. Understanding the post-translational modifications of TFEB is important for the development of diseases such as neurodegeneration and cancer.
Review
Biochemistry & Molecular Biology
Stephanie Vrijsen, Marine Houdou, Ana Cascalho, Jan Eggermont, Peter Vangheluwe
Summary: The polyamines putrescine, spermidine, and spermine play a vital role in mammalian cells and are tightly regulated by various mechanisms. This article discusses the balance between the neuroprotective and neurotoxic effects of polyamines in Parkinson's disease (PD). Polyamine levels decline with aging and are altered in PD patients, and recent studies suggest a disrupted polyamine homeostasis as a driving factor in PD. Polyamines influence PD pathogenesis, such as alpha-synuclein aggregation, and affect PD-related processes like autophagy, heavy metal toxicity, oxidative stress, neuroinflammation, and lysosomal/mitochondrial dysfunction. The article also highlights outstanding research questions regarding the role of polyamines in PD, their potential as biomarkers, and possible therapeutic strategies targeting polyamine homeostasis.
ANNUAL REVIEW OF BIOCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Sukhee Cho, Hyein Lee, Minkyo Jung, Kirim Hong, Seung-Hwa Woo, Young-Sam Lee, Byoung Joon Kim, Mi Young Jeon, Jinsoo Seo, Ji Young Mun
Summary: NMO is an autoimmune disease that targets astrocytes through the action of NMO-IgG against AQP4. Research shows that NMO-IgG induces structural alterations in astrocyte mitochondria, leading to impaired mitochondrial functions and dynamics, as well as changes in endoplasmic reticulum and lysosomes. The study using an in vitro human astrocyte model system with iPSCs technology provides insights into how NMO-IgG rearranges cellular organelles and affects their functions, offering opportunities for studying the pathophysiological mechanisms of NMO for potential therapeutic compounds targeting astrocytic abnormalities in patients with NMO.
Article
Neurosciences
Fatema Currim, Jyoti Singh, Anjali Shinde, Dhruv Gohel, Milton Roy, Kritarth Singh, Shatakshi Shukla, Minal Mane, Hitesh Vasiyani, Rajesh Singh
Summary: Parkinson's disease is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the brain. Mitochondrial dysfunction and dysfunction of the lysosomes play a role in the pathogenesis, affecting exosome release and autophagy flux. Maintaining mitochondrial function is crucial for lysosomal function and exosome release in PD.
MOLECULAR NEUROBIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Britney N. Lizama, Charleen T. Chu
Summary: Autophagy is crucial for cells to remove damaged components and is increasingly studied for its role in various diseases. Research on autophagy and mitochondrial quality control is expanding, particularly in relation to conditions like cancer, immune diseases, and neurodegenerative diseases.
MOLECULAR ASPECTS OF MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Shanikumar Goyani, Milton Roy, Rajesh Singh
Summary: TRIM-NHL proteins possess unique RNA binding ability and E3 ligase activity, playing crucial roles in cellular processes and potential involvement in various pathological conditions.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2021)
Article
Cell Biology
Paresh Prajapati, Dhruv Gohel, Anjali Shinde, Milton Roy, Kritarth Singh, Rajesh Singh
CELLULAR SIGNALLING
(2020)
Article
Biochemistry & Molecular Biology
Dhruv Gohel, Lakshmi Sripada, Paresh Prajapati, Fatema Currim, Milton Roy, Kritarth Singh, Anjali Shinde, Minal Mane, Darshan Kotadia, Flora Tassone, Nicolas Charlet-Berguerand, Rajesh Singh
Summary: This study analyzed the impact of CGG repeat expansion on mitochondrial miRNAs and cellular functions, highlighting the critical role of miR-320a in FXTAS pathology. Transfection of miR-320a mimic was found to restore mitochondrial functions and rescue cell death in cells expressing CGG permutation, indicating its potential therapeutic value in FXTAS.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Neurosciences
Fatema Currim, Jyoti Singh, Anjali Shinde, Dhruv Gohel, Milton Roy, Kritarth Singh, Shatakshi Shukla, Minal Mane, Hitesh Vasiyani, Rajesh Singh
Summary: Parkinson's disease is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the brain. Mitochondrial dysfunction and dysfunction of the lysosomes play a role in the pathogenesis, affecting exosome release and autophagy flux. Maintaining mitochondrial function is crucial for lysosomal function and exosome release in PD.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hitesh Vasiyani, Anjali Shinde, Milton Roy, Minal Mane, Kritarth Singh, Jyoti Singh, Dhruv Gohel, Fatema Currim, Khushali Vaidya, Mahesh Chhabria, Rajesh Singh
Summary: The study demonstrates that c-di-AMP can activate the type-1 IFN response in ER-negative breast cancer cells, which is correlated with STING expression. Furthermore, c-di-AMP induces mitochondrial-mediated cell death and inhibits clonogenicity of triple-negative breast cancer cells.
Article
Oncology
Anjali Shinde, Hyeryeon Jung, Hayun Lee, Kritarth Singh, Milton Roy, Dhruv Gohel, Han Byeol Kim, Minal Mane, Hitesh Vasiyani, Fatema Currim, Yu Ri Seo, Seojin Yang, Ara Cho, Eugene C. Yi, Rajesh Singh
Summary: The study shows that TNF-alpha can regulate the survival and proliferation of aggressive tumor cells by modulating the levels of critical assembly factors and subunits involved in mitochondrial respiratory chain supercomplexes organization and function, favoring the rewiring of mitochondrial metabolism towards anaplerosis to support the survival and proliferation of breast cancer cells. The results strongly suggest that TNF-alpha differentially regulates metabolic adaptation in ER/PR +ve (MCF-7) and ER/PR -ve (MDA-MB-231) cells by modulating the mitochondrial supercomplex assembly and activity.
CANCER & METABOLISM
(2021)
Review
Biochemistry & Molecular Biology
Milton Roy, Rajesh Singh
Summary: TRIMs, as RING domain-containing E3 ligases, are involved in regulating the NF-kappa B pathway and may lead to unique outcomes in different pathophysiological conditions.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Cell Biology
Paresh Prajapati, Wang-Xia Wang, Steven A. Pesina, Urim Geleta, Joe E. Springer
Summary: Sex plays a significant role in neuroinflammatory responses to traumatic brain injury (TBI), and inflammatory microRNAs (miRNAs) may contribute to the sexually dimorphic neuroinflammatory response.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2023)
Article
Cell Biology
Milton Roy, Kritarth Singh, Anjali Shinde, Jyoti Singh, Minal Mane, Sawani Bedekar, Yamini Tailor, Dhruv Gohel, Hitesh Vasiyani, Fatema Currim, Rajesh Singh
Summary: The study identified TRIM proteins as potential feedback regulators of the TNF-alpha-induced NF-kappa B pathway. TRIM15 was found to be a late response gene induced by TNF-alpha and inhibits the NF-kappa B pathway in human cell lines. It promotes turnover of K63-linked ubiquitin chains and inhibits the activity of TAK1 and TRIM8, thus regulating the proinflammatory NF-kappa B pathway.
CELLULAR SIGNALLING
(2022)
Review
Cell Biology
Shatakshi Shukla, Fatema Currim, Rajesh Singh
Summary: Exosomes play an important role in intercellular communication and maintaining cellular homeostasis during development and differentiation. Dysregulation in exosome-mediated communication can lead to developmental defects and chronic diseases. Exosomes are heterogeneous and can vary in size, membrane protein abundance, and cargo content. This review focuses on the latest developments in exosome biogenesis pathways, heterogeneity, selective cargo enrichment, and isolation techniques. Understanding the heterogeneity and selective cargo enrichment of extracellular vesicles may provide insights into disease severity and early prognosis, and specific subtypes of exosomes can be used as therapeutic tools and biomarkers for specific diseases.
BIOLOGY OF THE CELL
(2023)
Article
Biochemistry & Molecular Biology
Dhruv Gohel, Shatakshi Shukla, Wenson David Rajan, Bartosz Wojtas, Bozena Kaminska, Rajesh Singh
Summary: Stroke is a major cause of death and disabilities globally. Mitochondria play a critical role in inflammation and cell death, and mitochondrial dysfunction can lead to inflammatory responses. This study found that the pattern of miRNAs associated with mitochondrial functions changes under ischemic conditions, and the altered miRNAs target mitochondrial proteins involved in maintaining mitochondrial homeostasis.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Cell Biology
Gopal V. Velmurugan, W. Brad Hubbard, Paresh Prajapati, Hemendra J. Vekaria, Samir P. Patel, Alexander G. Rabchevsky, Patrick G. Sullivan
Summary: This study aimed to improve mitochondrial function after brain injury by targeting LDL receptor-related protein 1 (LRP1) and demonstrated it as a potential pharmacotherapeutic strategy. The results showed that oxidative stress increased mitochondrial quantity, while LRP1 deficiency significantly decreased mitochondrial fragmentation, preserving mitochondrial function and cell growth. Therefore, targeting LRP1 to improve mitochondrial function may be used for the treatment of traumatic brain injury and other neurodegenerative diseases.
Article
Cell Biology
Wang-Xia Wang, Paresh Prajapati, Hemendra J. Vekaria, Malinda Spry, Amber L. Cloud, Patrick G. Sullivan, Joe E. Springer
Summary: The study found that mitochondria-enriched miRNAs showed persistent alterations in injured hippocampal cells in rats after severe controlled cortical impact injury, while miRNAs not enriched in mitochondria did not exhibit significant changes in mitochondria. Nanoparticle delivery of miR-146a showed potential in modulating pro-inflammatory effectors in the injured brain.
NEURAL REGENERATION RESEARCH
(2021)