Effects of short-to-long term enzyme replacement therapy (ERT) on skeletal muscle tissue in late onset Pompe disease (LOPD).

Aims: Pompe disease is an autosomal recessive lysosomal storage disorder resulting from deficiency of acid α-glucosidase (GAA) enzyme. Histopathological hallmarks in skeletal muscle tissue are fibre vacuolization and autophagy. Since 2006, enzyme replacement therapy (ERT) is the only approved treatment with human recombinant GAA alglucosidase alfa.

Regulation and involvement of the ubiquitin ligases in muscle atrophy.

The ability to activate compensatory mechanisms in response to environmental stress is an important factor for survival and maintenance of cellular functions. A system that is often activated both in short and prolonged stress conditions is ubiquitin proteasome system (UPS). UPS is required to clear the cell from dysfunctional and altered proteins and is reported to increase during catabolic conditions.

The mitochondrial calcium uniporter controls skeletal muscle trophism in vivo.

Muscle atrophy contributes to the poor prognosis of many pathophysiological conditions, but pharmacological therapies are still limited. Muscle activity leads to major swings in mitochondrial [Ca(2+)], which control aerobic metabolism, cell death, and survival pathways. We investigated in vivo the effects of mitochondrial Ca(2+) homeostasis in skeletal muscle function and trophism by overexpressing or silencing the mitochondrial calcium uniporter (MCU).

Deficient nitric oxide signalling impairs skeletal muscle growth and performance: involvement of mitochondrial dysregulation.

Background: Nitric oxide (NO), generated in skeletal muscle mostly by the neuronal NO synthases (nNOSμ), has profound effects on both mitochondrial bioenergetics and muscle development and function. The importance of NO for muscle repair emerges from the observation that nNOS signalling is defective in many genetically diverse skeletal muscle diseases in which muscle repair is dysregulated. How the effects of NO/nNOSμ on mitochondria impact on muscle function, however, has not been investigated yet.

Electrical stimulation counteracts muscle decline in seniors.

The loss in muscle mass coupled with a decrease in specific force and shift in fiber composition are hallmarks of aging. Training and regular exercise attenuate the signs of sarcopenia. However, pathologic conditions limit the ability to perform physical exercise.

Haptoglobin is required to prevent oxidative stress and muscle atrophy.

Background: Oxidative stress (OS) plays a major role on tissue function. Several catabolic or stress conditions exacerbate OS, inducing organ deterioration. Haptoglobin (Hp) is a circulating acute phase protein, produced by liver and adipose tissue, and has an important anti-oxidant function.

Signalling pathways regulating muscle mass in ageing skeletal muscle: the role of the IGF1-Akt-mTOR-FoxO pathway.

During ageing skeletal muscles undergo a process of structural and functional remodelling that leads to sarcopenia, a syndrome characterized by loss of muscle mass and force and a major cause of physical frailty. To determine the causes of sarcopenia and identify potential targets for interventions aimed at mitigating ageing-dependent muscle wasting, we focussed on the main signalling pathway known to control protein turnover in skeletal muscle, consisting of the insulin-like growth factor 1 (IGF1), the kinase Akt and its downstream effectors, the mammalian target of rapamycin (mTOR) and the transcription factor FoxO. Expression analyses at the transcript and protein level, carried out on well-characterized cohorts of young, old sedentary and old active individuals and on mice aged 200, 500 and 800 days, revealed only modest age-related differences in this pathway.

Mitochondrial biogenesis and fragmentation as regulators of protein degradation in striated muscles.

Mitochondria are dynamic organelles which adapt their morphology by fusion and fission events to the bioenergetic requirements of the cell. Cardiac and skeletal muscles are tissues with high energy demand and mitochondrial plasticity plays a key role in the homeostasis of these cells. Indeed, alterations in mitochondrial morphology, distribution and function are common features in catabolic conditions.

Mitochondrial biogenesis and fragmentation as regulators of muscle protein degradation.

Mitochondria form a dynamic network that rapidly adapts to cellular energy demand. This adaptation is particularly important in skeletal muscle because of its high metabolic rate. Indeed, muscle energy level is one of the cellular checkpoints that lead either to sustained protein synthesis and growth or protein breakdown and atrophy.

Mitochondrial fission and remodelling contributes to muscle atrophy.

Mitochondria are crucial organelles in the production of energy and in the control of signalling cascades. A machinery of pro-fusion and fission proteins regulates their morphology and subcellular localization. In muscle this results in an orderly pattern of intermyofibrillar and subsarcolemmal mitochondria.

Improvement of a FRET-based indicator for cAMP by linker design and stabilization of donor-acceptor interaction.

Förster resonance energy transfer (FRET) technology has been used to develop genetically encoded fluorescent indicators for a variety of intracellular molecular events. Often, however, the poor dynamic range of such reporters prevents detection of subtle but physiologically relevant signals. Here we present a strategy for improving FRET efficiency between donor and acceptor fluorophores in a green fluorescent protein (GFP)-based protein indicator for cAMP.