Review
Pharmacology & Pharmacy
Yanhong Song, Ziyi Wu, Ping Zhao
Summary: This article discusses the potential of using metformin in the treatment of osteoarthritis, highlighting its benefits in inhibiting inflammation, modulating autophagy, antagonizing oxidative stress, and reducing pain levels for patients. Metformin, with its anti-inflammatory and anti-aging properties, has the potential to be an effective drug for treating osteoarthritis.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Neurosciences
Vishakh Iyer, Kala Venkiteswaran, Sandip Savaliya, Christopher A. Lieu, Erin Handly, Timothy P. Gilmour, Allen R. Kunselman, Thyagarajan Subramanian
Summary: Parkinson's disease (PD) is a neurodegenerative disorder commonly treated with levodopa, which can lead to levodopa-induced dyskinesias (LID). This study found that the survival of the cross-hemispheric nigrostriatal pathway plays a crucial role in preventing the expression of LID in PD, suggesting it could be a potential target for preventing this devastating side effect.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Medicine, Research & Experimental
Gui Cao, Ting Gong, Yue Du, Yicun Wang, Tongtong Ge, Jingyu Liu
Summary: Metformin, a first-line drug for the treatment of type 2 diabetes mellitus (T2DM), has been widely studied. It has been found to have potential neuroprotective and regulatory effects on the central nervous system (CNS), in addition to its known benefits for diabetes management.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Clinical Neurology
Koji Furukawa, Atsushi Shima, Daisuke Kambe, Akira Nishida, Ikko Wada, Haruhi Sakamaki, Kenji Yoshimura, Yuta Terada, Yusuke Sakato, Masahiro Mitsuhashi, Masanori Sawamura, Etsuro Nakanishi, Yosuke Taruno, Hodaka Yamakado, Yasutaka Fushimi, Tomohisa Okada, Yuji Nakamoto, Ryosuke Takahashi, Nobukatsu Sawamoto
Summary: This study investigates the correlation between motor impairments and striatal dopaminergic terminal degeneration and nigral neuromelanin-laden dopamine neuron loss in different stages of Parkinson's disease. The findings suggest that striatal dopaminergic terminal loss is a biomarker for early stage motor impairments, while nigral dopamine neuron loss is a biomarker for advanced stage motor impairments.
ANNALS OF NEUROLOGY
(2022)
Article
Clinical Neurology
Han-Kyeol Kim, Tae Won Kim, Min Seok Baek, Eung Yeop Kim, Young Hee Sung, Jae Hoon Lee, Young Hoon Ryu, Sung Jun Ahn, Han Soo Yoo, Chul Hyoung Lyoo
Summary: In this study, the visibility of NG1 in SMwI was found to be associated with the degree of nigrostriatal degeneration in PD patients. It was concluded that SMwI can be used for diagnosing PD only after the onset of motor symptoms.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Laura A. Struzyna, Kevin D. Browne, Justin C. Burrell, Wisberty J. Gordian Velez, Kathryn L. Wofford, Hilton M. Kaplan, N. Sanjeeva Murthy, H. Isaac Chen, John E. Duda, Rodrigo A. Espana, D. Kacy Cullen
Summary: This study successfully created a tissue-engineered nigrostriatal pathway (TE-NSP) using microtissue engineering techniques. The implanted TE-NSP showed survival, dopamine release, and integration with host tissue in a rat PD model, providing a potential strategy for replacing lost neuroarchitecture in PD patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Rakesh Kumar Majhi, Soumitra Mohanty, Witchuda Kamolvit, John Kerr White, Andrea Scheffschick, Hanna Brauner, Annelie Brauner
Summary: Metformin enhances innate immunity of uroepithelial cells by activating macrophages, inducing enhanced intracellular and extracellular bacterial killing, thus playing a favorable role in host defense.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Jared Senfeld, Qianman Peng, Yi Shi, Shenqi Qian, Jianzhong Shen
Summary: Metformin, which has been the first-line therapy for diabetes for almost 70 years, has a controversial mechanism of action. A new study found that metformin blocks high glucose-stimulated ATP secretion, thus exerting its antihyperglycemic effect. The study also revealed that the purinergic antidiabetic mechanism of metformin involves the inhibition of P2Y(2) receptors, which is similar to the effects observed when these receptors are removed.
Article
Medicine, Research & Experimental
Tongtong Zhang, Xiang Yin, Xuefan Yu, Ren Shang, Liuzhe Lu, Jing Miao
Summary: This study summarizes the clinical features of three GNE patients with the p.D207V mutation and describes the pathogenesis of GNE myopathy and the significance of metformin in this disease. The results show that metformin protects GNE fibroblasts by restoring autophagic flux and through the AMPK/mTOR-independent pathway.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Cell Biology
Miao He, Bangbao Lu, Michael Opoku, Liang Zhang, Wenqing Xie, Hongfu Jin, Siyu Chen, Yusheng Li, Zhenhan Deng
Summary: This review comprehensively summarizes the current research progress on metformin as a proposed drug for the prevention or treatment of osteoarthritis, including its molecular mechanism and clinical significance.
Article
Chemistry, Multidisciplinary
Jiang-Peng Fan, Hui-Zhen Geng, Ya-Wei Ji, Tao Jia, Jennifer B. Treweek, An-An Li, Chun-Yi Zhou, Viviana Gradinaru, Cheng Xiao
Summary: Key components in the nigrostriatal DA system exhibit distinct aging patterns and may contribute to age-related alterations in locomotion and coordination.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Multidisciplinary Sciences
Kotaro Tokuda, Yoshiaki Yamanaka, Yosuke Mano, Manabu Tsukamoto, Takafumi Tajima, Hitoshi Suzuki, Makoto Kawasaki, Soshi Uchida, Eiichiro Nakamura, Ke-Yong Wang, Akinori Sakai
Summary: This study demonstrated that metformin treatment can effectively suppress joint capsular fibrosis, with the most effective time for administration being early after joint immobilization; a delay of more than 2 weeks of administration will result in reduced effectiveness.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Marine Lacomme, Sarah C. Hales, Thomas W. Brown, Katarina Stevanovic, Christine Jolicoeur, Jenny Cai, Therence Bois, Melissa Desrosiers, Deniz Dalkara, Michel Cayouette
Summary: This study reveals Numb as a key regulator of intracellular Tau levels and identifies Numb-72 as a potential therapeutic factor for tauopathies.
Article
Multidisciplinary Sciences
Ahmet Karatas, Burak Oz, Cigdem Celik, Zeynel Abidin Akar, Ramazan Fazil Akkoc, Ebru Onalan Etem, Adile Ferda Dagli, Suleyman Serdar Koca
Summary: This study aimed to investigate the therapeutic efficacy of tofacitinib and metformin on inflammation and fibrosis in a mouse model of systemic sclerosis. The results showed that tofacitinib and metformin can mitigate dermal fibrosis, reduce IL-17 and TGF-beta levels, and have anti-inflammatory and anti-fibrotic effects.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Nick G. Hollon, Elora W. Williams, Christopher D. Howard, Hao Li, Tavish Traut, Xin Jin
Summary: Dopamine encodes cue-reward prediction errors during Pavlovian conditioning, but its role in controlling sequential behavior remains largely unknown. Previous studies primarily use discrete reward-predictive stimuli, and it is still unclear whether dopamine represents action-outcome prediction errors.
Article
Cell Biology
Kaitlin R. Morrison, William J. Smiles, Naomi X. Y. Ling, Ashfaqul Hoque, Gabrielle Shea, Kevin R. W. Ngoei, Dingyi Yu, Lisa Murray-Segal, John W. Scott, Sandra Galic, Bruce. E. Kemp, Janni Petersen, Jonathan S. Oakhill
Summary: AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1) are metabolic kinases that co-ordinate nutrient supply with cell growth. This study reveals an α2-specific mechanism by which AMPK can be activated at lysosomes in the absence of changes in cellular energy. Loss of α2-S345 phosphorylation in endogenous AMPK fails to sustain cell growth under amino acid starvation conditions.
Review
Cell Biology
Martina Sassi, Alwena H. Morgan, Jeffrey S. Davies
Summary: Adult hippocampal neurogenesis is impaired in aging and neurodegenerative disorders. Ghrelin, a gut hormone, plays a role in regulating this process. The acylated form of ghrelin stimulates neurogenesis, while the unacylated form inhibits it. Restoring acyl-ghrelin signaling may promote memory function activation.
Article
Biochemistry & Molecular Biology
Ashley J. Ovens, Yi Sing Gee, Naomi X. Y. Ling, Dingyi Yu, Justin P. Hardee, Jin D. Chung, Kevin R. W. Ngoei, Nicholas J. Waters, Nolan J. Hoffman, John W. Scott, Kim Loh, Katrin Spengler, Regine Heller, Michael W. Parker, Gordon S. Lynch, Fei Huang, Sandra Galic, Bruce E. Kemp, Jonathan B. Baell, Jonathan S. Oakhill, Christopher G. Langendorf
Summary: AMPK is a cellular energy sensor and regulator of energy homeostasis. Activating AMPK shows potential for treating type 2 diabetes and insulin resistance. Recent studies suggest that the ??202??1 isoform combination is primarily responsible for these effects. Structure/function analysis of SC4 activator led to the discovery of MSG010 and MSG011, which show greater potency in activating ??202??1 AMPK compared to MK-8722. These findings guide the development of selective AMPK activators.
BIOCHEMICAL JOURNAL
(2022)
Article
Physiology
Natalie R. Janzen, Jamie Whitfield, Lisa Murray-Segal, Bruce E. Kemp, John A. Hawley, Nolan J. Hoffman
Summary: Disrupting AMPK-glycogen interaction reduces maximal exercise capacity and skeletal muscle AMPK alpha and beta 2 content, and increases glycogen utilization.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Endocrinology & Metabolism
Olivia R. Ghosh-Swaby, Amy C. Reichelt, Paul A. S. Sheppard, Jeffrey Davies, Timothy J. Bussey, Lisa M. Saksida
Summary: This article discusses the role of metabolic hormones in neural plasticity and cognition, as well as the relationship between metabolic hormones and metabolic syndromes such as obesity and diabetes. Adjusting metabolic hormone levels can restore metabolic homeostasis and enhance cognitive function.
FRONTIERS IN NEUROENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Brittany A. Stork, Adam Dean, Andrea R. Ortiz, Pradip Saha, Nagireddy Putluri, Maricarmen D. Planas-Silva, Iqbal Mahmud, Kimal Rajapakshe, Cristian Coarfa, Stefan Knapp, Philip L. Lorenzi, Bruce E. Kemp, Benjamin E. Turk, John W. Scott, Anthony R. Means, Brian York
Summary: CaMKK2 plays a central role as a metabolic fuel sensor in the liver, contributing significantly to whole body systems metabolism. The study reveals that CaMKK2 ablation improves peripheral insulin sensitivity by promoting glucose metabolism through phosphorylation and regulation of GAPDH, and by reducing peroxisomal fatty acid catabolism through modulation of PEX3.
MOLECULAR METABOLISM
(2022)
Article
Endocrinology & Metabolism
Man K. S. Lee, Olivia D. Cooney, Xuzhu Lin, Shaktypreya Nadarajah, Dragana Dragoljevic, Kevin Huynh, Danise-Ann Onda, Sandra Galic, Peter J. Meikle, Thomas Edlund, Morgan D. Fullerton, Bruce E. Kemp, Andrew J. Murphy, Kim Loh
Summary: The study revealed that the AMPK/HMGCR axis plays a crucial role in the development of atherosclerosis. Defects in AMPK regulation of HMGCR lead to increased aortic lesions, plaque-associated macrophages, lipid accumulation, and atherogenic monocytes.
MOLECULAR METABOLISM
(2022)
Article
Medicine, Research & Experimental
Geoff Harley, Marina Katerelos, Kurt Gleich, David P. de Souza, Vinod K. Narayana, Bruce E. Kemp, David A. Power, Peter F. Mount
Summary: The phosphorylation of ACC plays a crucial role in regulating cellular energy metabolism in acute kidney injury. The diabetes drug metformin has a protective effect against acute kidney injury, but this effect is absent in mice with impaired fatty acid metabolism. Metabolomic analysis shows that metformin affects multiple metabolic pathways related to kidney injury.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Behavioral Sciences
Helen J. Rushby, Zane B. Andrews, Matthew D. W. Piper, Christen K. Mirth
Summary: Modifying the proportions of macronutrients in the diet has significant effects on the reproduction and health of animals. In this study, using capillary feeding assays, we explored how adult fruit flies compromise their nutrient intake when limited to single diets. We found that young male and female flies compromised by consuming more food on diets with low protein to carbohydrate ratios. Additionally, female flies showed greater variations in carbohydrate intake compared to males, and mated females consumed more food than virgin females.
Article
Endocrinology & Metabolism
Romana Stark, Jack Feehan, Aya Mousa, Zane B. B. Andrews, Barbora de Courten
Summary: This study identified an association between liver-expressed antimicrobial peptide 2 (LEAP2) levels and key cardiometabolic risk factors in individuals with overweight and obesity, including body fat, insulin secretion, and insulin resistance. LEAP2 may represent a potential therapeutic target to promote insulin secretion in individuals with type 2 diabetes and obesity.
DIABETES OBESITY & METABOLISM
(2023)
Article
Biology
Kaixin Huang, Laura K. Milton, Harry Dempsey, Stephen J. Power, Kyna-Anne Conn, Zane B. Andrews, Claire J. Foldi
Summary: Anorexia nervosa is a psychiatric disorder with a high mortality rate. Cognitive inflexibility is associated with the disorder, but it is unclear whether it predisposes individuals to anorexia nervosa. Previous animal studies using the activity-based anorexia model have shown a link between cognitive inflexibility and pathological weight loss. However, testing flexible learning in the same animals before exposure to the activity-based anorexia model has been difficult. This study presents a fully-automated and experimenter-free touchscreen cognitive testing system for rats and examines the relationship between reversal learning and weight loss in the activity-based anorexia model. The findings provide insights into the connection between cognitive inflexibility and pathological weight loss and offer potential targets for future research on pharmacotherapies for anorexia nervosa.
Article
Endocrinology & Metabolism
Felicia Reed, Alex Reichenbach, Harry Dempsey, Rachel E. Clarke, Mathieu Mequinion, Romana Stark, Sasha Rawlinson, Claire J. Foldi, Sarah H. Lockie, Zane B. Andrews
Summary: This study reveals that hunger and the environmental context can increase food-seeking behavior, and the activity of AgRP neurons plays a crucial role in this process. Precise temporal control of AgRP neuron activity is necessary for the development of the context-induced feeding response.
MOLECULAR METABOLISM
(2023)
Article
Endocrinology & Metabolism
Wang Lok So, Jiachen Hu, Lotus Jeffs, Harry Dempsey, Sarah H. Lockie, Jeffrey M. Zigman, Romana Stark, Alex Reichenbach, Zane B. Andrews
Summary: The sensory detection of food suppresses AgRP neuronal activity, and ghrelin receptor signaling on AgRP neurons integrates energy need with external sensory cues to produce an optimal change in AgRP neural activity.
MOLECULAR METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Luke D. Roberts, Amanda K. E. Hornsby, Alanna Thomas, Martina Sassi, Aimee Kinzett, Nathan Hsiao, Bethan R. David, Mark Good, Timothy Wells, Jeffrey S. Davies
Article
Biochemical Research Methods
M. Carla Carisi, Owain W. Howell, Alwena H. Morgan, Jeffrey S. Davies
Summary: The article describes a modified protocol for RNA in situ hybridization on fixed-frozen human brain tissue, which improves tissue stability and stain quality.