Correction for ‘Green reduction of graphene oxide mediated by Sporosarcina pasteurii under harsh conditions, changing the paradigm of rGO production with a non-pathogenic, nanomaterial-resistant bacterium’ by Massimiliano Papi et al. , Green Chem. , 2026, 28 , 6317–6331, https://doi.org/10.1039/D5GC04774A.

The interest of lipid vesicles for applications in the pharmaceutical field is increasing, especially for preparing drug and gene delivery vectors. There are different methods for the preparation of these vesicles, however, microfluidic-based methods provide significant advantages over other synthetic protocols like extrusion and sonication. In this study, monodisperse liposomes based on L-α-phosphatidylcholine were synthesized using a versatile capillary hydrodynamic flow-focusing device to deliver verbascoside into murine C2C12 muscle cells. The size and surface charge of the obtained liposomes were studied using Dynamic Light Scattering (DLS) and zeta-potential measurements. TEM and SAXS analyses were used to investigate the shape and lamellarity of the structures. By introducing a suitable dye into the phospholipid membrane of the liposomes and using confocal fluorescence microscopic analysis, liposomes internalization in C2C12 cells was confirmed in vitro. In addition, verbascoside encapsulation in the vesicles protected it efficiently, increasing its antioxidant activity against ROS production in C2C12 cells.

The stability of the sarcolemma is severely impaired in a series of genetic neuromuscular diseases defined as muscular dystrophies. These are characterized by the centralization of skeletal muscle syncytial nuclei, the replacement of muscle fibers with fibrotic tissue, the release of inflammatory cytokines, and the disruption of muscle protein homeostasis, ultimately leading to necrosis and loss of muscle functionality. A specific subgroup of muscular dystrophies is associated with genetic defects in components of the dystrophin–glycoprotein complex (DGC), which plays a crucial role in linking the cytosol to the skeletal muscle basement membrane. In these cases, dystrophin-associated proteins fail to correctly localize to the sarcolemma, resulting in dystrophy characterized by an uncontrolled increase in protein degradation, which can ultimately lead to cell death. In this review, we explore the role of intracellular degradative pathways—primarily the ubiquitin–proteasome and autophagy–lysosome systems—in the progression of DGC-linked muscular dystrophies. The DGC acts as a hub for numerous signaling pathways that regulate various cellular functions, including protein homeostasis. We examine whether the loss of structural stability within the DGC affects key signaling pathways that modulate protein recycling, with a particular emphasis on autophagy.

IntroductionDystroglycan (DG) is an adhesion complex comprising two subunits, α-DG and β-DG, which interact non-covalently at the plasma membrane. As a component of the dystrophin-glycoprotein complex DGC, DG plays a crucial role in linking the cytoskeleton to the surrounding basement membranes. Rare primary point mutations in the DAG1 gene have been identified in patients with various forms of neuromuscular dystrophy, ranging in phenotype from mild to severe.MethodsTo gain a deeper understanding of the molecular mechanisms underlying these pathologies, we have designed a series of chimeric GFP-tagged full-length α/β-DG constructs and expressed them in three different cell lines (U-2OS, HEK-293T and C2C12). Wild-type DG constructs were compared to their counterparts carrying pathologic missense mutations previously described in patients, namely, L84F, T190M and C667F and with the mutant I591D, i.e., the topological equivalent of V567D identified in zebrafish.ResultsLive super-resolution fluorescence microscopy showed that the C667F mutant is retained within the ER/Golgi while the T190M and wild-type proteins are correctly localized to the plasma membrane in all 3 cell lines. The L84F mutant exhibits a delay in trafficking to the plasma membrane in two of the cell lines, while localizing strongly at the plasma membrane in the high-expression HEK-293T cells. Similarly, the I591D mutant accumulated at the plasma membrane in the HEK-293T cells, in contrast to the clear retention in the endoplasmic reticulum/Golgi apparatus observed in U-2OS and C2C12 cells.DiscussionOur data demonstrate the importance of using a range of different cell lines for a comprehensive study of DG mutants or variants by live cell optical super-resolution microscopy.

Dystroglycan (DG) is an extracellular matrix receptor consisting of an α- and a β-DG subunit encoded by the DAG1 gene. The homozygous mutation (c.2006G>T, p.Cys669Phe) in β-DG causes muscle-eye-brain disease with multicystic leukodystrophy in humans. In a mouse model of this primary dystroglycanopathy, approximately two-thirds of homozygous embryos fail to develop to term. Mutant mice that are born undergo a normal postnatal development but show a late-onset myopathy with partially penetrant histopathological changes and an impaired performance on an activity wheel. Their brains and eyes are structurally normal, but the localization of mutant β-DG is altered in the glial perivascular end-feet, resulting in a perturbed protein composition of the blood-brain and blood-retina barrier. In addition, α- and β-DG protein levels are significantly reduced in muscle and brain of mutant mice. Owing to the partially penetrant developmental phenotype of the C669F β-DG mice, they represent a novel and highly valuable mouse model with which to study the molecular effects of β-DG functional alterations both during embryogenesis and in mature muscle, brain and eye, and to gain insight into the pathogenesis of primary dystroglycanopathies.

In the current study, a new series of N-acetylpyrazolines (6a-d) were designed and synthesized from their corresponding chalcones and hydrazine hydrate in acidic medium. The N-acetylpyrazolines (6a-d) were tested for their anti-hepatocellular activity against liver cancer (Huh-7, and HepG-2), and normal BNL cell lines and compared with paclitaxel, colchicine, and combrestatin A-4 (CA-4), as standards, and their IC50 values were determined. The 3',4',5'-trimethoxyphenyl N-acetylpyrazoline derivative 6d was the found the most potent N-acetylpyrazoline derivative IC50 = 0.30, and 77.30 mu M, respectively, and found non-cytotoxic to the normal BNL cell line. While compounds 6b, and 6c revealed lower anticancer activity against Huh-7 cell line IC50 = 14.50, and 11.00 mu M, respectively. Moreover, the N-acetylpyrazolines 6a-d were evaluated for their anticancer screening against different cancer cell lines at 10 mu M by the Developmental Therapeutic Program (DTP) - NCI - USA, and they showed mean GI% ranges 8.87-64.54%. The 3',4',5'-trimethoxyphenyl N-acetylpyrazolines 6c, and 6d revealed potent anticancer activities and lethal effects against lung cancer cell line (HOP-92) for 6c and melanoma cell line (SK-MEL-5) for 6d with GI% values of 104.80, and 109.52%, respectively. Furthermore, the N-acetylpyrazolines 6a-d enhanced tublin polymerization, and showed tubulin-stabilizing effects as paclitaxel at 50 mu M. A molecular docking study was performed for the N-acetylpyrazolines 6a-d to investigate the binding pattern at the Taxol-binding site of microtubules.

In recent years, the use of MXenes, a class of two-dimensional materials composed of transition metal carbides, nitrides, or carbonitrides, has shown significant promise in the field of skin wound healing. This review explores the multifunctional properties of MXenes, focusing on their electrical conductivity, photothermal effects, and biocompatibility in this field. MXenes have been utilized to develop advanced wound healing devices such as hydrogels, patches, and smart bandages for healing examination. These devices offer enhanced antibacterial activity, promote tissue regeneration, and provide real-time monitoring of parameters. The review highlights the synthesis methods, chemical features, and biological effects of MXenes, emphasizing their role in innovative skin repair strategies. Additionally, it discusses the potential of MXene-based sensors for humidity, pH, and temperature monitoring, which are crucial for preventing infections and complications in wound healing. The integration of MXenes into wearable devices represents a significant advancement in wound management, promising improved clinical outcomes and enhanced quality of life for patients.

Dystroglycan (DG) is a cell adhesion complex that is widely expressed in tissues. It is composed by two subunits, a-DG, a highly glycosylated protein that interacts with several extracellular matrix proteins, and transmembrane 13-DG whose, cytodomain binds to the actin cytoskeleton. Glycosylation of a-DG is crucial for functioning as a receptor for its multiple extracellular binding partners. Perturbation of a-DG glycosylation is the central event in the pathogenesis of severe pathologies such as muscular dystrophy and cancer. 13-DG acts as a scaffold for several cytoskeletal and nuclear proteins and very little is known about the fine regulation of some of these intracellular interactions and how they are perturbed in diseases. To start filling this gap by identifying uncharacterized intracellular networks preferentially associated with 13-DG, HEK-293 cells were transiently transfected with a plasmid carrying the 13-DG subunit with GFP fused at its C-terminus. With this strategy, we aimed at forcing 13-DG to occupy multiple intracellular locations instead of sitting tightly at its canonical plasma membrane milieu, where it is commonly found in association with a-DG. Immunoprecipitation by anti-GFP antibodies followed by shotgun proteomic analysis led to the identification of an interactome formed by 313 exclusive protein matches for 13-DG binding. A series of already known 13-DG interactors have been found, including ezrin and emerin, whilst significant new matches, which include potential novel 13-DG interactors and their related networks, were identified in diverse subcellular compartments, such as cytoskeleton, endoplasmic reticulum/Golgi, mitochondria, nuclear membrane and the nucleus itself. Of particular interest amongst the novel identified matches, Lamina-Associated Polypeptide-1B (LAP1B), an inner nuclear membrane protein, whose mutations are known to cause nuclear envelopathies characterized by muscular dystrophy, was found to interact with 13-DG in HEK-293 cells. This evidence was confirmed by immunoprecipitation, Western blotting and immunofluorescence experiments. We also found by immunofluorescence experiments that LAP1B looses its nuclear envelope localization in C2C12 DG-knock-out cells, suggesting that LAP1B requires 13-DG for a proper nuclear localization. These results expand the role of 13-DG as a nuclear scaffolding protein and provide novel evidence of a possible link between dystroglycanopathies and nuclear envelopathies displaying with muscular dystrophy.

In the current study, two series of novel thiazolidin-4-one benzenesulfonamide arylidene hybrids 9a -l and 10a -f were designed, synthesized and tested in vitro for their PPARy agonistic activity. The phenethyl thiazolidin-4-one sulphonamide 9l showed the highest PPARy activation % by 41.7%. Whereas, the 3-methoxyand 4methyl-4-benzyloxy thiazolidin-4-one sulphonamides 9i, and 9k revealed moderate PPARy activation % of 31.7, and 32.8%, respectively, in addition, the 3-methoxy3-benzyloxy thiazolidin-4-one sulphonamide 10d showed PPARy activation % of 33.7% compared to pioglitazone. Compounds 9b, 9i, 9k, 9l, and 10d revealed higher selectivity to PPARy over the PPAR delta, and PPAR alpha isoforms. An immunohistochemical study was performed in HepG-2 cells to confirm the PPARy protein expression for the most active compounds. Compounds 9i, 9k, and 10d showed higher PPARy expression than that of pioglitazone. Pharmacological studies were also performed to determine the anti-diabetic activity in rats at a dose of 36 mg/kg, and it was revealed that compounds 9i and 10d improved insulin secretion as well as anti-diabetic effects. The 3-methoxy-4-benzyloxy thiazolidin-4-one sulphonamide 9i showed a better anti-diabetic activity than pioglitazone. Moreover, it showed a rise in blood insulin by 4-folds and C -peptide levels by 48.8%, as well as improved insulin sensitivity. Moreover, compound 9i improved diabetic complications as evidenced by decreasing liver serum enzymes, restoration of total protein and kidney functions. Besides, it combated oxidative stress status and exerted anti- hyperlipidemic effect. Compound 9i showed a superior activity by normalizing some parameters and amelioration of pancreatic, hepatic, and renal histopathological alterations caused by STZ-induction of diabetes. Molecular docking studies, molecular dynamic simulations, and protein ligand interaction analysis were also performed for the newly synthesized compounds to investigate their predicted binding pattern and energies in PPARy binding site.

The pressing need for multifunctional materials in medical settings encompasses a wide array of scenarios, necessitating specific tissue functionalities. A critical challenge is the occurrence of biofouling, particularly by contamination in surgical environments, a common cause of scaffolds impairment. Beyond the imperative to avoid infections, it is also essential to integrate scaffolds with living cells to allow for tissue regeneration, mediated by cell attachment. Here, we focus on the development of a versatile material for medical applications, driven by the diverse time-definite events after scaffold implantation. We investigate the potential of incorporating graphene oxide (GO) into polycaprolactone (PCL) and create a composite for 3D printing a scaffold with time-controlled antibacterial and anti-adhesive growth properties. Indeed, the as-produced PCL-GO scaffold displays a local hydrophobic effect, which is translated into a limitation of biological entities-attachment, including a diminished adhesion of bacteriophages and a reduction of E. coli and S. aureus adhesion of ∼81% and ∼69%, respectively. Moreover, the ability to 3D print PCL-GO scaffolds with different heights enables control over cell distribution and attachment, a feature that can be also exploited for cellular confinement, i.e., for microfluidics or wound healing applications. With time, the surface wettability increases, and the scaffold can be populated by cells. Finally, the presence of GO allows for the use of infrared light for the sterilization of scaffolds and the disruption of any bacteria cell that might adhere to the more hydrophilic surface. Overall, our results showcase the potential of PCL-GO as a versatile material for medical applications.

Dystroglycan (DG) is a cell adhesion complex that is widely expressed in tissues. It is composed by two subunits, α-DG, a highly glycosylated protein that interacts with several extracellular matrix proteins, and transmembrane β-DG whose, cytodomain binds to the actin cytoskeleton. Glycosylation of α-DG is crucial for functioning as a receptor for its multiple extracellular binding partners. Perturbation of α-DG glycosylation is the central event in the pathogenesis of severe pathologies such as muscular dystrophy and cancer. β-DG acts as a scaffold for several cytoskeletal and nuclear proteins and very little is known about the fine regulation of some of these intracellular interactions and how they are perturbed in diseases. To start filling this gap by identifying uncharacterized intracellular networks preferentially associated with β-DG, HEK-293 cells were transiently transfected with a plasmid carrying the β-DG subunit with GFP fused at its C-terminus. With this strategy, we aimed at forcing β-DG to occupy multiple intracellular locations instead of sitting tightly at its canonical plasma membrane milieu, where it is commonly found in association with α-DG. Immunoprecipitation by anti-GFP antibodies followed by shotgun proteomic analysis led to the identification of an interactome formed by 313 exclusive protein matches for β-DG binding. A series of already known β-DG interactors have been found, including ezrin and emerin, whilst significant new matches, which include potential novel β-DG interactors and their related networks, were identified in diverse subcellular compartments, such as cytoskeleton, endoplasmic reticulum/Golgi, mitochondria, nuclear membrane and the nucleus itself. Of particular interest amongst the novel identified matches, Lamina-Associated Polypeptide-1B (LAP1B), an inner nuclear membrane protein, whose mutations are known to cause nuclear envelopathies characterized by muscular dystrophy, was found to interact with β-DG in HEK-293 cells. This evidence was confirmed by immunoprecipitation, Western blotting and immunofluorescence experiments. We also found by immunofluorescence experiments that LAP1B looses its nuclear envelope localization in C2C12 DG-knock-out cells, suggesting that LAP1B requires β-DG for a proper nuclear localization. These results expand the role of β-DG as a nuclear scaffolding protein and provide novel evidence of a possible link between dystroglycanopathies and nuclear envelopathies displaying with muscular dystrophy.

Muscle weakness and muscle loss characterize many physio-pathological conditions, including sarcopenia and many forms of muscular dystrophy, which are often also associated with mitochondrial dysfunction. Verbascoside, a phenylethanoid glycoside of plant origin, also named acteoside, has shown strong antioxidant and anti-fatigue activity in different animal models, but the molecular mechanisms underlying these effects are not completely understood. This study aimed to investigate the influence of verbascoside on mitochondrial function and its protective role against H2O2-induced oxidative damage in murine C2C12 myoblasts and myotubes pre-treated with verbascoside for 24 h and exposed to H2O2. We examined the effects of verbascoside on cell viability, intracellular reactive oxygen species (ROS) production and mitochondrial function through high-resolution respirometry. Moreover, we verified whether verbascoside was able to stimulate nuclear factor erythroid 2-related factor (Nrf2) activity through Western blotting and confocal fluorescence microscopy, and to modulate the transcription of its target genes, such as heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), by Real Time PCR. We found that verbascoside (1) improved mitochondrial function by increasing mitochondrial spare respiratory capacity; (2) mitigated the decrease in cell viability induced by H2O2 and reduced ROS levels; (3) promoted the phosphorylation of Nrf2 and its nuclear translocation; (4) increased the transcription levels of HO-1 and, in myoblasts but not in myotubes, those of PGC-1α. These findings contribute to explaining verbascoside’s ability to relieve muscular fatigue and could have positive repercussions for the development of therapies aimed at counteracting muscle weakness and mitochondrial dysfunction.

Dystroglycan (DG) is a glycoprotein and extracellular matrix receptor consisting of an α-DG and a β-DG subunit encoded by the gene DAG1 . A homozygous missense mutation (c.2006G>T), resulting in an amino acid substitution (p.Cys669Phe) in the extracellular domain of β-DG, causes severe Muscle-Eye-Brain disease with multicystic leukodystrophy. To investigate the mechanisms underlying the severe human pathology, we generated a mouse model of this primary dystroglycanopathy. We find that homozygous mutant mice show no obvious abnormalities during development and reach mature adulthood. However, α- and β-DG protein levels are significantly downregulated in muscle and brain of homozygous mutant mice. The mutant mice show a form of myopathy with late-onset and not fully penetrant histopathological changes in skeletal muscle and are impaired in their performance on an activity wheel. The brain and eyes of the homozygous mutant mice appear to be structurally normal, but the localization of mutant β-DG is altered in the glial perivascular endfeet (PVE) at the blood-brain- and blood-retina barrier resulting in a perturbed protein composition in the PVE. In conclusion, the mouse model of the C669F β-DG mutation does not seem to recapitulate the severe developmental phenotypes observed in human patients but represents a novel and highly valuable tool to study the impact of β-DG functional changes at the molecular level and to gain insight into the pathogenesis of primary dystroglycanopathies.

Dystroglycan (DG) is a transmembrane protein widely expressed in multiple cells and tissues. It is formed by two subunits, α− and β-DG, and represents a molecular bridge between the outside and the inside of the cell, which is essential for the mechanical and structural stability of the plasma membrane. The α-subunit is a cell-surface protein that binds to the extracellular matrix (ECM) and is tightly associated with the plasma membrane via a non-covalent interaction with the β-subunit, which, in turn, is a transmembrane protein that binds to the cytoskeletal actin. DG is a versatile molecule acting not only as a mechanical building block but also as a modulator of outside–inside signaling events. The cytoplasmic domain of β-DG interacts with different adaptor and cytoskeletal proteins that function as molecular switches for the transmission of ECM signals inside the cells. These interactions can modulate the involvement of DG in different biological processes, ranging from cell growth and survival to differentiation and proliferation/regeneration. Although the molecular events that characterize signaling through the ECM-DG-cytoskeleton axis are still largely unknown, in recent years, a growing list of evidence has started to fill the gaps in our understanding of the role of DG in signal transduction. This mini-review represents an update of recent developments, uncovering the dual role of DG as an adhesion and signaling molecule that might inspire new ideas for the design of novel therapeutic strategies for pathologies such as muscular dystrophy, cardiomyopathy, and cancer, where the DG signaling hub plays important roles.

Additive manufacturing has played a crucial role in the COVID-19 global emergency allowing for rapid production of medical devices, indispensable tools for hospitals, or personal protection equipment. However, medical devices, especially in nosocomial environments, represent high touch surfaces prone to viral infection and currently used filaments for 3D printing can't inhibit transmission of virus [1]. Graphene-family materials are capable of reinforcing mechanical, optical and thermal properties of 3D printed constructs. In particular, graphene can adsorb near-infrared light with high efficiency. Here we demonstrate that the addition of graphene nanoplatelets to PLA filaments (PLA-G) allows the creation of 3D-printed devices that can be sterilized by near-infrared light exposure at power density analog to sunlight. This method has been used to kill SARS-CoV-2 viral particles on the surface of 3D printed PLA-G by 3 min of exposure. 3D-printed PLA-G is highly biocompatible and can represent the ideal material for the production of sterilizable personal protective equipment and daily life objects intended for multiple users.(c) 2022 Elsevier Ltd. All rights reserved.

Aiming to discover new antihyperlipidemic agents, a new set of quinazolinone-fibrate hybrids 9a-r bearing the essential features for peroxisome proliferator-activated receptor-α (PPARα) agonistic activity was synthesized and the structures were confirmed by different spectral data. All the target compounds were screened for their PPARα agonistic activity. Compounds 9o and 9q exhibited potent activity, with EC50 values better than that of fenofibrate by 8.7- and 27-fold, respectively. Molecular docking investigations were performed for all the newly synthesized compounds in the active site of the PPARα receptor to study their interactions and energies in the receptor. Moreover, the antihyperlipidemic and antioxidant activities of compounds 9o and 9q were determined using Triton WR-1339-induced hyperlipidemic rats. Compound 9q exhibited effective hypolipidemic activity in a dose-dependent manner, where it significantly reduced the serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol and increased the level of high-density lipoprotein cholesterol. Furthermore, it possesses a powerful antioxidant profile where it significantly elevated the levels of reduced glutathione as well as the total antioxidant capacity and significantly decreased the malondialdehyde level. The histopathological studies revealed that compound 9q improved the aortic architecture and hepatic steatosis. These findings support that compound 9q could be a promising lead compound for the development of new antihyperlipidemic agents.

In the current work, a series of novel 4-benzyloxy and 4-(2-phenylethoxy) chalcone fibrate hybrids (10a-o) and (11a-e) were synthesized and evaluated as new PPAR alpha agonists in order to find new agents with higher activity and fewer side effects. The 2-propanoic acid derivative 10a and the 2-butanoic acid congener 10i showed the best overall PPARa agonistic activity showing E-max% values of 50.80 and 90.55%, respectively, and EC50 values of 8.9 and 25.0 mu M, respectively, compared to fenofibric acid with E-max = 100% and EC50 = 23.22 mu M, respectively. These two compounds also stimulated carnitine palmitoyltransferase 1A gene transcription in HepG2 cells and PPAR alpha protein expression. Molecular docking simulations were performed for the newly synthesized compounds to study their predicted binding pattern and energies in PPAR alpha active site to rationalize their promising activity. In vivo, compounds 10a and 10i elicited a significant hypolipidemic activity improving the lipid profile in triton WR-1339-induced hyperlipidemic rats, including serum triglycerides, total cholesterol, LDL, HDL and VLDL levels. Compound 10i possessed better anti-hyperlipidemic activity than 10a. At a dose of 200 mg/kg, it demonstrated significantly lower TC, TG, LDL and VLDL levels than that of fenofibrate at the same dose with similar HDL levels. Compounds 10i and 10a possessed atherogenic indices (CRR, AC, AI, CRI-II) like that of fenofibrate. Additionally, a promising antioxidant activity indicated by the increased tissue reduced glutathione and plasma total antioxidant capacity with decreased plasma malondialdehyde levels was demonstrated by compounds 10a and 10i. No histopathological alterations were recorded in the hepatic tissue of compound 10i (200 mg/kg).

The acetylglucosaminyltransferase-like protein LARGE1 is an enzyme that is responsible for the final steps of the post-translational modifications of dystroglycan (DG), a membrane receptor that links the cytoskeleton with the extracellular matrix in the skeletal muscle and in a variety of other tissues. LARGE1 acts by adding the repeating disaccharide unit [-3Xyl-α1,3GlcAβ1-] to the extracellular portion of the DG complex (α-DG); defects in the LARGE1 gene result in an aberrant glycosylation of α-DG and consequent impairment of its binding to laminin, eventually affecting the connection between the cell and the extracellular environment. In the skeletal muscle, this leads to degeneration of the muscular tissue and muscular dystrophy. So far, a few missense mutations have been identified within the LARGE1 protein and linked to congenital muscular dystrophy, and because no structural information is available on this enzyme, our understanding of the molecular mechanisms underlying these pathologies is still very limited. Here, we generated a 3D model structure of the two catalytic domains of LARGE1, combining different molecular modeling approaches. Furthermore, by using molecular dynamics simulations, we analyzed the effect on the structure and stability of the first catalytic domain of the pathological missense mutation S331F that gives rise to a severe form of muscle-eye-brain disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by pathogenic expansions of the triplet cytosine-adenosine-guanosine (CAG) within the Huntingtin gene. These expansions lead to a prolongation of the poly-glutamine stretch at the N-terminus of Huntingtin causing protein misfolding and aggregation. Huntingtin and its pathological variants are widely expressed, but the central nervous system is mainly affected, as proved by the wide spectrum of neurological symptoms, including behavioral anomalies, cognitive decline and motor disorders. Other hallmarks of HD are loss of body weight and muscle atrophy. This review highlights some key elements that likely provide a major contribution to muscle atrophy, namely, alteration of the transcriptional processes, mitochondrial dysfunction, which is strictly correlated to loss of energy homeostasis, inflammation, apoptosis and defects in the processes responsible for the protein quality control. The improvement of muscular symptoms has proven to slow the disease progression and extend the life span of animal models of HD, underlining the importance of a deep comprehension of the molecular mechanisms driving deterioration of muscular tissue.