Publications
High mitochondrial calcium levels precede neuronal death in vivo in Alzheimer’s disease
June 18, 2020
MITOCHONDRIAL CALCIUM OVERLOAD AFTER PLAQUE DEPOSITION Ca2+ is essential for the normal function of mitochondrial activity, and therefore Ca2+ levels are tightly regulated in mitochondria. However, excessive levels of Ca2+
The role of lipids in autophagy and its implication in neurodegeneration
May 19, 2020
Neurodegenerative diseases are, at present, major socio-economic burdens without effective treatments and their increasing prevalence means that these diseases will be a challenge for future generations. Neurodegenerative diseases may differ in etiology and pathology but are often caused by the accumulation of dysfunctional and aggregation-prone proteins. Autophagy, a conserved cellular mechanism, deals with cellular stress and waste product build-up and has been shown to reduce the accumulation of dysfunctional proteins in animal models of neurodegenerative diseases. Historically, progress in understanding the precise function of lipids has traditionally been far behind other biological molecules (like proteins) but emerging works demonstrate the importance of lipids in the autophagy pathway and how the disturbance of lipid metabolism is connected to neurodegeneration. Here we review how altered autophagy and the disturbance of lipid metabolism, particularly of phosphoinositols and sphingolipids, feature in neurodegenerative diseases and address work from the field that suggests that these potentially offer an opportunity of therapeutic intervention.
Immune system activation by natural products and complex fractions: a network pharmacology approach in cancer treatment
May 18, 2020
INTRODUCTION Over the past decade, immunotherapy has become a promising approach to treat cancer and is now being combined with standard chemotherapy and immune response activators to improve the outcome
HIF1α or mitophagy: which drives cardiomyocyte differentiation?
May 10, 2020
Cardiomyocytes (CMs) are the main cellular component of the heart's atria and ventricles, and their contractile capacity is the engine that drives blood flow throughout the body. The differentiation of
Copper – a novel stimulator of autophagy
April 24, 2020
In biomedicine, the transition metal copper has a Janus-faced dual role, as an essential but static cofactor of vital enzymes but also as a highly detrimental poison, if in excess.
Towards understanding the role of Receptor Expression Enhancing Protein 5 (REEP5) in cardiac muscle and beyond
April 15, 2020
DISCOVERY OF REEP5 Cardiac membrane proteins play an important role in regulating normal beat-to-beat function of the heart given their importance in coordinating spontaneous contractions of cardiomyocytes in the heart.
Role of RNA Binding Proteins with prion-like domains in muscle and neuromuscular diseases
March 10, 2020
A number of neuromuscular and muscular diseases, including amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA) and several myopathies, are associated to mutations in related RNA-binding proteins (RBPs), including TDP-43, FUS, MATR3 or hnRNPA1/B2. These proteins harbor similar modular primary sequence with RNA binding motifs and low complexity domains, that enables them to phase separate and create liquid microdomains. These RBPs have been shown to critically regulate multiple events of RNA lifecycle, including transcriptional events, splicing and RNA trafficking and sequestration. Here, we review the roles of these disease-related RBPs in muscle and motor neurons, and how their dysfunction in these cell types might contribute to disease.
HIF1α-dependent mitophagy facilitates cardiomyoblast differentiation
March 4, 2020
Mitophagy is thought to play a key role in eliminating damaged mitochondria, with diseases such as cancer and neurodegeneration exhibiting defects in this process. Mitophagy is also involved in cell differentiation and maturation, potentially through modulating mitochondrial metabolic reprogramming. Here we examined mitophagy that is induced upon iron chelation and found that the transcriptional activity of HIF1α, in part through upregulation of BNIP3 and NIX, is an essential mediator of this pathway in SH-SY5Y cells. In contrast, HIF1α is dispensable for mitophagy occurring upon mitochondrial depolarisation. To examine the role of this pathway in a metabolic reprogramming and differentiation context, we utilised the H9c2 cell line model of cardiomyocyte maturation. During differentiation of these cardiomyoblasts, mitophagy increased and required HIF1α-dependent upregulation of NIX. Though HIF1α was essential for expression of key (...)