Article
Biochemistry & Molecular Biology
Leticia Perez-Sisques, Julia Solana-Balaguer, Genis Campoy-Campos, Nuria Martin-Flores, Anna Sancho-Balsells, Marcel Vives-Isern, Ferran Soler-Palazon, Marta Garcia-Forn, Merce Masana, Jordi Alberch, Esther Perez-Navarro, Albert Giralt, Cristina Malagelada
Summary: RTP801 is increased in neurodegenerative diseases and its downregulation can improve behavioral abnormalities. This study found that RTP801 levels are increased in the hippocampus of HD patients, correlated with gliosis markers. Silencing RTP801 in the dorsal hippocampus of HD mouse models improved cognitive alterations and reduced inflammation.
Article
Cell Biology
Julia Solana-Balaguer, Nuria Martin-Flores, Pol Garcia-Segura, Genis Campoy-Campos, Leticia Perez-Sisques, Almudena Chicote-Gonzalez, Joaquin Fernandez-Irigoyen, Enrique Santamaria, Esther Perez-Navarro, Jordi Alberch, Cristina Malagelada
Summary: This study investigates the transfer of RTP801 toxicity via extracellular vesicles (EVs), and its impact on neuronal death and morphology. Results indicate that RTP801-induced toxicity is transferred to neurons via EVs, leading to apoptosis and impairing neuron morphology complexity. Conversely, EVs derived from neurons where RTP801 was silenced show improved arborization in recipient neurons.
JOURNAL OF EXTRACELLULAR VESICLES
(2023)
Review
Biochemistry & Molecular Biology
William P. Miller, Siddharth Sunilkumar, Michael D. Dennis
Summary: Diabetic Retinopathy (DR) is primarily caused by oxidative stress, with the stress response protein REDD1 playing a key role by regulating the cell's response through mTORC1. Additionally, REDD1 acts independently of mTORC1 to promote oxidative stress by enhancing reactive oxygen species production and suppressing antioxidant responses. Early clinical trials targeting REDD1 mRNA with siRNA have shown some success in combating ischemic retinal disease, indicating the potential for novel therapies targeting the underlying molecular mechanisms of DR.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Medicine, Research & Experimental
Zong-Bao Yan, Jin-Yu Zhang, Yi-Pin Lv, Wen-Qing Tian, Zhi-Guo Shan, Fang-Yuan Mao, Yu-Gang Liu, Wan-Yan Chen, Pan Wang, Yun Yang, Ping Cheng, Liu-Sheng Peng, Ya-Ling Liao, Geng-Yu Yue, Xiao-Lin Xu, Yong-Liang Zhao, Mu-Han Lu, Yuan Zhuang
Summary: The study found that REDD1 is increased in the gastric mucosa of H. pylori-infected patients and mice. H. pylori induced GECs to express REDD1 via the phosphorylated cagA, activating the MAPKp38 pathway. In Redd1-/- mice, gastric inflammation, MHCII+ monocyte infiltration, IL-23, and IL-17A were all attenuated.
Editorial Material
Multidisciplinary Sciences
Zak Doric, Ken Nakamura
Summary: By disrupting mitochondria in vulnerable neuronal cells, mice provide a new model of Parkinson's disease that challenges long-held ideas about the disease's motor symptoms.
Article
Neurosciences
Leticia Perez-Sisques, Nuria Martin-Flores, Merce Masana, Julia Solana-Balaguer, Arnau Llobet, Joan Romani-Aumedes, Merce Canal, Genis Campoy-Campos, Esther Garcia-Garcia, Nuria Sanchez-Fernandez, Sara Fernandez-Garcia, James P. Gilbert, Manuel Jose Rodriguez, Heng-Ye Man, Elena Feinstein, David L. Williamson, David Soto, Xavier Gasull, Jordi Alberch, Cristina Malagelada
Summary: The study reveals the crucial role of RTP801 in neuronal plasticity and motor learning. Knockdown of RTP801 enhances excitatory synaptic transmission and improves motor learning, while also regulating spine density and synaptic-related protein levels.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Cell Biology
Hyeon-Ok Jin, Sung-Eun Hong, Ji-Young Kim, Se-Kyeong Jang, In-Chul Park
Summary: Amino acid deprivation induces the activation of GCN2/ATF4/REDD1 axis, leading to AKT activation and promoting the survival signal in cancer cells. REDD1 plays a crucial role in the response of cells to amino acid deprivation and radiotherapy.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Siddharth Sunilkumar, Allyson L. Toro, Christopher M. McCurry, Ashley M. VanCleave, Shaunaci A. Stevens, William P. Miller, Scot R. Kimball, Michael D. Dennis
Summary: The study revealed that REDD1 plays a crucial role in diabetes-induced retinal inflammation by enhancing the activation of the NF-KB signaling pathway to increase the expression of inflammatory cytokines.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Endocrinology & Metabolism
Lin Mu, Nan Chen, Yakun Chen, Zhifen Yang, Huandi Zhou, Shan Song, Yonghong Shi
Summary: This study found that REDD1 was elevated in DN patients and diabetic mice, and REDD1 deficiency significantly improved apoptosis and EMT in DN mice. It was also discovered that inhibiting REDD1 could suppress the synthesis of Nox4 and ROS induced by HG.
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY
(2022)
Editorial Material
Cell Biology
Shree Padma Metur, Daniel J. Klionsky
Summary: Maintaining mitochondrial quality control is crucial for neuronal homeostasis, and dysregulation of this process has been implicated in neurodegenerative diseases. This study demonstrates that neurons sustain axonal mitophagy by locally translating Pink1 mRNA that is co-transported with mitochondria to the distal axons, providing a continuous supply of PINK1 protein.
Article
Multidisciplinary Sciences
Safa Salim, Fatima Ahmad, Ayesha Banu, Farhan Mohammad
Summary: Parkinson's disease (PD) is caused by ⍺-synuclein aggregation-mediated dopaminergic neuronal loss, leading to motor and non-motor symptoms. Inflammation-mediated oxidative stress, mitochondrial dysfunction, and cytokine-induced toxicity are believed to be involved in the neuronal damage and loss associated with PD. The gut and brain have been found to play important roles in the pathogenesis of PD. This review summarizes the impact of gut microbiome alterations on PD pathogenesis and proposes early interventions and dietary modifications as potential protective measures against PD development.
JOURNAL OF ADVANCED RESEARCH
(2023)
Review
Clinical Neurology
Kaitlyn M. L. Cramb, Dayne Beccano-Kelly, Stephanie J. Cragg, Richard Wade-Martins
Summary: Cramb et al. provide a review of evidence suggesting dopamine release deficits occur prior to neurodegeneration in Parkinson's disease. They also highlight the need for further investigation in understanding the mechanisms behind these deficits.
Article
Neurosciences
Jie Xu, Yun-Lin Ao, Chunhui Huang, Xiubao Song, Guiliang Zhang, Wei Cui, Yuqiang Wang, Xiao-Qi Zhang, Zaijun Zhang
Summary: This study found that harmol can reduce the abnormal accumulation of α-synuclein in Parkinson's disease through the activation of the AMPK-mTOR-TFEB-mediated autophagy pathway. In vitro and in vivo experiments showed that harmol can improve motor impairment and lower α-synuclein levels, suggesting its potential benefit in the treatment of Parkinson's disease.
NPJ PARKINSONS DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Ifat Alsharif, Loubna Boukhzar, Benjamin Lefranc, David Godefroy, Juliette Aury-Landas, Jean-Luc do Rego, Jean-Claude do Rego, Frederic Naudet, Arnaud Arabo, Abdeslam Chagraoui, David Maltete, Abdelhamid Benazzouz, Catherine Bauge, Jerome Leprince, Abdel G. Elkahloun, Lee E. Eiden, Youssef Anouar
Summary: PSELT, derived from SELENOT, shows promise as a therapeutic candidate for Parkinson's disease by targeting oxidative stress at multiple intracellular levels.
Review
Biochemistry & Molecular Biology
Karim E. Shalaby, Omar M. A. El-Agnaf
Summary: Gene therapy has the potential to replace current treatments for Parkinson's disease and has been shown to be safe and effective in current trials.
Article
Cell Biology
Nuria Martin-Flores, Leticia Perez-Sisques, Jordi Creus-Muncunill, Merce Masana, Silvia Gines, Jordi Alberch, Esther Perez-Navarro, Cristina Malagelada
CELL DEATH & DISEASE
(2020)
Article
Clinical Neurology
Ying Fan, Raja S. Nirujogi, Alicia Garrido, Javier Ruiz-Martinez, Alberto Bergareche-Yarza, Elisabet Mondragon-Rezola, Ana Vinagre-Aragon, Ioana Croitoru, Ana Gorostidi Pagola, Laura Paternain Markinez, Roy Alcalay, Richard A. Hickman, Jonas During, Sara Gomes, Neringa Pratuseviciute, Shalini Padmanabhan, Francesc Valldeoriola, Leticia Perez Sisques, Cristina Malagelada, Teresa Ximelis, Laura Molina Porcel, Maria Jose Marti, Eduardo Tolosa, Dario R. Alessi, Esther M. Sammler
Summary: This study found a significant increase in pRab10(Thr73) phosphorylation in carriers of the LRRK2 R1441G mutation, whereas the effect of the LRRK2 G2019S mutation was not statistically significant. Analysis of pRab10(Thr73) phosphorylation in post-mortem brain samples revealed high variability mainly due to the adverse effects of the peri- and post-mortem period on protein phosphorylation stability.
ACTA NEUROPATHOLOGICA
(2021)
Article
Neurosciences
Leticia Perez-Sisques, Nuria Martin-Flores, Merce Masana, Julia Solana-Balaguer, Arnau Llobet, Joan Romani-Aumedes, Merce Canal, Genis Campoy-Campos, Esther Garcia-Garcia, Nuria Sanchez-Fernandez, Sara Fernandez-Garcia, James P. Gilbert, Manuel Jose Rodriguez, Heng-Ye Man, Elena Feinstein, David L. Williamson, David Soto, Xavier Gasull, Jordi Alberch, Cristina Malagelada
Summary: The study reveals the crucial role of RTP801 in neuronal plasticity and motor learning. Knockdown of RTP801 enhances excitatory synaptic transmission and improves motor learning, while also regulating spine density and synaptic-related protein levels.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Cell Biology
Leticia Perez-Sisques, Anna Sancho-Balsells, Julia Solana-Balaguer, Genis Campoy-Campos, Marcel Vives-Isern, Ferran Soler-Palazon, Marta Anglada-Huguet, Miguel-Angel Lopez-Toledano, Eva-Maria Mandelkow, Jordi Alberch, Albert Giralt, Cristina Malagelada
Summary: RTP801 protein levels are increased in postmortem hippocampal samples from AD patients, correlating with disease progression and GFAP expression. Downregulation of RTP801 in mouse models improves cognitive deficits and reverses gliosis hallmarks and inflammasome proteins. This suggests that RTP801 could be a potential future therapeutic target for AD, serving as a biomarker of neuroinflammation severity and a promising target for treatment.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Leticia Perez-Sisques, Julia Solana-Balaguer, Genis Campoy-Campos, Nuria Martin-Flores, Anna Sancho-Balsells, Marcel Vives-Isern, Ferran Soler-Palazon, Marta Garcia-Forn, Merce Masana, Jordi Alberch, Esther Perez-Navarro, Albert Giralt, Cristina Malagelada
Summary: RTP801 is increased in neurodegenerative diseases and its downregulation can improve behavioral abnormalities. This study found that RTP801 levels are increased in the hippocampus of HD patients, correlated with gliosis markers. Silencing RTP801 in the dorsal hippocampus of HD mouse models improved cognitive alterations and reduced inflammation.
Article
Biochemistry & Molecular Biology
Ernest Palomer, Nuria Martin-Flores, Sarah Jolly, Patricia Pascual-Vargas, Stefano Benvegnu, Marina Podpolny, Samuel Teo, Kadi Vaher, Takashi Saito, Takaomi C. Saido, Paul Whiting, Patricia C. Salinas
Summary: Growing evidence suggests the involvement of deficient Wnt signaling in Alzheimer's disease (AD). This study highlights the role of Wnt receptors Fzd1 and Fzd7 in AD progression and identifies nuclear hyperactivated SIRT2 as a potential target for AD treatment.
MOLECULAR PSYCHIATRY
(2022)
Article
Clinical Neurology
Alicia Garrido, Leticia Perez-Sisques, Cristina Simonet, Genis Campoy-Campos, Julia Solana-Balaguer, Nuria Martin-Flores, Manel Fernandez, Marta Soto, Donina Obiang, Ana Camara, Francesc Valldeoriola, Esteban Munoz, Yaroslau Compta, Esther Perez-Navarro, Jordi Alberch, Eduardo Tolosa, Maria-Jose Marti, Mario Ezquerra, Cristina Malagelada, Ruben Fernandez-Santiago
Summary: The purpose of this study was to investigate whether differential phosphorylation states of blood markers can identify patients with LRRK2 Parkinson's disease (PD). It was found that there were specific increases of P-Ser-473-AKT levels in all G2019S carriers, either L2PD or L2NMC, absent in iPD.
ANNALS OF NEUROLOGY
(2022)
Editorial Material
Biochemistry & Molecular Biology
Pol Garcia-Segura, Cristina Malagelada
Summary: A novel repression mechanism of the transcription factor STAT3 over the REDD1 gene, called DDIT4, has been identified. These findings are crucial for understanding the stress-induced short-lived REDD1 protein, which inactivates mTOR, and its potential impact in pathological conditions such as cancer or neurodegenerative diseases.
Article
Multidisciplinary Sciences
Megan E. Jones, Johanna Buchler, Tom Dufor, Ernest Palomer, Samuel Teo, Nuria Martin-Flores, Katharina Boroviak, Emmanouil Metzakopian, Alasdair Gibb, Patricia C. Salinas
Summary: Synapse loss in Alzheimer's disease (AD) is associated with cognitive decline, but the mechanisms are not well understood. Reduced Wnt signaling, due to the variant LRP6 receptor (LRP6-Val), contributes to synapse dysfunction and loss in AD. Mice carrying the Lrp6-Val variant show synaptic defects and become more vulnerable to synapse loss with age and in the presence of AD pathology. This study reveals a previously unrecognized role of Lrp6-Val in synapse vulnerability during aging and AD.
Article
Cell Biology
Julia Solana-Balaguer, Genis Campoy-Campos, Nuria Martin-Flores, Leticia Perez-Sisques, Laia Sitja-Roqueta, Melike Kucukerden, Ana Gamez-Valero, Albert Coll-Manzano, Eulalia Marti, Esther Perez-Navarro, Jordi Alberch, Jordi Soriano, Merce Masana, Cristina Malagelada
Summary: Extracellular vesicles, specifically neuron-derived EVs, play a crucial role in intercellular communication within the central nervous system. These EVs carry signaling molecules and exert a trophic effect on neurons, influencing synaptic events and promoting neuronal protection.
JOURNAL OF EXTRACELLULAR VESICLES
(2023)
Article
Cell Biology
Julia Solana-Balaguer, Nuria Martin-Flores, Pol Garcia-Segura, Genis Campoy-Campos, Leticia Perez-Sisques, Almudena Chicote-Gonzalez, Joaquin Fernandez-Irigoyen, Enrique Santamaria, Esther Perez-Navarro, Jordi Alberch, Cristina Malagelada
Summary: This study investigates the transfer of RTP801 toxicity via extracellular vesicles (EVs), and its impact on neuronal death and morphology. Results indicate that RTP801-induced toxicity is transferred to neurons via EVs, leading to apoptosis and impairing neuron morphology complexity. Conversely, EVs derived from neurons where RTP801 was silenced show improved arborization in recipient neurons.
JOURNAL OF EXTRACELLULAR VESICLES
(2023)
Article
Neurosciences
Faye McLeod, Kieran Boyle, Aude Marzo, Nuria Martin-Flores, Thaw Zin Moe, Ernest Palomer, Alasdair J. Gibb, Patricia C. Salinas
FRONTIERS IN SYNAPTIC NEUROSCIENCE
(2020)