A5088924127- Muscle Physiology and Disorders
- Histone Deacetylase Inhibitors Research
- Adipose Tissue and Metabolism
- Exercise and Physiological Responses
- Epigenetics and DNA Methylation
- Autophagy in Disease and Therapy
- Neurogenetic and Muscular Disorders Research
- Nutrition and Health in Aging
- Protein Degradation and Inhibitors
- Amyotrophic Lateral Sclerosis Research
- Sirtuins and Resveratrol in Medicine
- Muscle metabolism and nutrition
- Ubiquitin and proteasome pathways
- Heat shock proteins research
- Genetic Neurodegenerative Diseases
- Genetics and Neurodevelopmental Disorders
- Neuroendocrine regulation and behavior
- MicroRNA in disease regulation
- Genetics and Physical Performance
- RNA Research and Splicing
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Pluripotent Stem Cells Research
- Children's Physical and Motor Development
- Mesenchymal stem cell research
Istituto di Nanotecnologia
2021-2025
Sapienza University of Rome
2014-2023
National Research Council
2021-2023
Institut de Myologie
2013-2018
IRCCS Ospedale San Raffaele
2017-2018
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2017-2018
Institute of Macromolecular Chemistry
2010-2012
The University of Texas Southwestern Medical Center
2009-2012
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by loss of motor neurons, denervation target muscles, muscle atrophy, and paralysis. Understanding ALS pathogenesis may require fuller understanding the bidirectional signaling between neurons skeletal fibers at neuromuscular synapses. Here, we show that key regulator this miR-206, muscle-specific microRNA dramatically induced in mouse model ALS. Mice are genetically deficient miR-206 form normal synapses during...
microRNAs (miRNAs) play key roles in modulating a variety of cellular processes through repression mRNA targets. In screen for miRNAs regulated by myocardin-related transcription factor-A (MRTF-A), coactivator serum response factor (SRF), we discovered muscle-enriched miRNA, miR-486, controlled an alternative promoter within intron 40 the Ankyrin-1 gene. Transcription miR-486 is directly SRF and MRTF-A, as well MyoD. Among most strongly predicted targets are phosphatase tensin homolog (PTEN)...
Abstract Recent studies have correlated physical activity with a better prognosis in cachectic patients, although the underlying mechanisms are not yet understood. In order to identify pathways involved activity-mediated rescue of skeletal muscle mass and function, we investigated effects voluntary exercise on cachexia colon carcinoma (C26)-bearing mice. Voluntary prevented loss ultimately increasing survival C26-bearing We found that autophagic flux is overloaded both murine models but...
Maintenance of skeletal muscle structure and function requires efficient precise metabolic control. Autophagy plays a key role in homeostasis diverse tissues by recycling cellular constituents, particularly under conditions caloric restriction, thereby normalizing metabolism. Here we show that histone deacetylases (HDACs) 1 2 control autophagy flux mice. Skeletal muscle-specific deletion both HDAC1 HDAC2 results perinatal lethality subset mice, accompanied mitochondrial abnormalities...
Chronic disease states are associated with elevated levels of inflammatory cytokines that have been demonstrated to lead severe muscle wasting. A mechanistic understanding wasting is hampered by limited in vivo cytokine models which can be applied emerging mouse mutants as they generated. We developed a simple and novel approach induce adult skeletal based on direct gene transfer an expression vector encoding the secreted form murine tumor necrosis factor-alpha (mTNFalpha). This procedure...
Abstract Heat shock protein 60 (Hsp60) is a chaperone localizing in skeletal muscle mitochondria, whose role poorly understood. In the present study, levels of Hsp60 fibres entire posterior group hindlimb muscles ( gastrocnemius , soleus and plantaris ) were evaluated mice after completing 6-week endurance training program. The correlation between expression four isoforms peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) investigated only . Short-term...
Cellular senescence is a permanent state of replicative arrest defined by specific pattern gene expression. The epigenome in senescent cells sculptured order to sustain the new transcriptional requirements, particularly at enhancers and super-enhancers. How these distal regulatory elements are dynamically modulated not completely defined.Enhancer regions presence H3K27 acetylation marks, which can be class IIa HDACs, as part multi-protein complexes. Here, we explore regulation HDACs...
Alzheimer’s disease (AD), a debilitating neurodegenerative disorder, remains one of the foremost public health challenges affecting more than 30 million people worldwide with etiology still largely enigmatic. The intricate gut-brain axis, serving as vital communication network between gut and brain, appears to wield influence in progression AD. Our study showcases remarkable precision x-ray phase-contrast tomography (XPCT) conducting an advanced three-dimensional examination cellular...
Emerging evidence suggests that the muscle microenvironment plays a prominent role in cancer cachexia. We recently showed NF‐kB‐induced Pax7 overexpression impairs myogenic potential of precursors cachectic mice, suggesting lowering expression may be beneficial evaluated regenerative after acute injury C26 colon carcinoma tumor‐bearing mice and healthy controls. Our analyses confirmed delayed regeneration observed muscles form was associated with persistent local inflammation overexpression....
Histone deacetylase 4 (HDAC4) has been proposed as a target for Amyotrophic Lateral Sclerosis (ALS) because it mediates nerve-skeletal muscle interaction and since its expression in skeletal correlates with the severity of disease. However, our recent studies on response upon long-term denervation highlighted importance HDAC4 maintaining integrity.To fully identify yet uncharacterized functions ALS, we genetically deleted muscles mouse model ALS. Body weight, muscle, innervation spinal cord...
Abstract Skeletal muscle is susceptible to injury following trauma, neurological dysfunction, and genetic diseases. homeostasis maintained by a pronounced regenerative capacity, which includes the recruitment of stem cells. Chronic exposure tumor necrosis factor-α (TNF) triggers wasting reminiscent cachexia. To better understand effects TNF upon cells, we exposed injured at specific time points during regeneration. delayed appearance regenerating fibers, without exacerbating fiber death...
Muscle homeostasis involves de novo myogenesis, as observed in conditions of acute or chronic muscle damage. Tumor Necrosis Factor (TNF) triggers skeletal wasting several pathological and inhibits regeneration. We show that intramuscular treatment with the myogenic factor Arg(8)-vasopressin (AVP) enhanced regeneration rescued inhibitory effects TNF on The functional analysis regenerating performance following AVP treatments revealed these factors exerted opposite function. Principal...
Skeletal muscle exhibits a high regenerative capacity, mainly due to the ability of satellite cells replicate and differentiate in response appropriate stimuli. Epigenetic control is effective at different stages this process. It has been shown that chromatin-remodeling factor HDAC4 able regulate cell proliferation commitment. However, its molecular targets are still uncovered. To explain signaling pathways regulated by cells, we generated tamoxifen-inducible mice with conditional...
The development of therapeutic strategies for skeletal muscle diseases, such as physical injuries and myopathies, depends on the knowledge regulatory signals that control myogenic process. obestatin/GPR39 system operates an autocrine signal in regulation myogenesis. Using a mouse model regeneration after injury several cellular strategies, we explored potential use obestatin agent treatment trauma-induced injuries. Our results evidenced overexpression preproghrelin, thus obestatin, GPR39...
An idiopathic myopathy characterized by central nuclei in muscle fibers, a hallmark of regeneration, has been observed cancer patients. In cachexia skeletal is incapable consequently, this observation remains unaccounted for. C26-tumor bearing, cachectic mice, we fibers with the absence molecular markers bona fide regeneration. These clustered, non-peripheral were present NCAM-expressing fibers. Since NCAM expression upregulated denervated myofibers, searched for additional makers...
Denervation triggers numerous molecular responses in skeletal muscle, including the activation of catabolic pathways and oxidative stress, leading to progressive muscle atrophy. Histone deacetylase 4 (HDAC4) mediates response denervation, suggesting use HDAC inhibitors as a therapeutic approach neurogenic However, effects HDAC4 inhibition long-term denervation have not been described yet. To further study functions we analyzed mutant mice which is specifically deleted muscle. After an...