Altered Metabolism in Motor Neuron Diseases: Mechanism and Potential Therapeutic Target

Barone, Cinzia; Qi, Xin

doi:10.3390/cells12111536

Cited by 2 publications

(1 citation statement)

References 128 publications

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“…Since MQC, i.e., the regulation and maintenance of mitochondrial homeostasis, is essential not only for the fine-tuning of cell energy production [115] but also for overall cellular health, mitochondrial dysfunction and inadequate QC inevitably lead to metabolic disorders in many pathological conditions [116,117]. Defective MQC has been associated with diseases of the heart [118], lung [119,120], and kidneys [121], and in neuronal and muscular disorders [122]. Further, the metabolic switch from ATP production by oxidative phosphorylation to aerobic glycolysis (the Warburg effect) is one of the underlining mechanisms of cancer cell proliferation, allowing transformed cells to adjust and grow in a poorly oxygenated milieu [123].…”

Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

Therapeutic Effects of Mesenchymal Stromal Cells Require Mitochondrial Transfer and Quality Control

Mukkala,

Jerkic,

Khan

et al. 2023

IJMS

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Due to their beneficial effects in an array of diseases, Mesenchymal Stromal Cells (MSCs) have been the focus of intense preclinical research and clinical implementation for decades. MSCs have multilineage differentiation capacity, support hematopoiesis, secrete pro-regenerative factors and exert immunoregulatory functions promoting homeostasis and the resolution of injury/inflammation. The main effects of MSCs include modulation of immune cells (macrophages, neutrophils, and lymphocytes), secretion of antimicrobial peptides, and transfer of mitochondria (Mt) to injured cells. These actions can be enhanced by priming (i.e., licensing) MSCs prior to exposure to deleterious microenvironments. Preclinical evidence suggests that MSCs can exert therapeutic effects in a variety of pathological states, including cardiac, respiratory, hepatic, renal, and neurological diseases. One of the key emerging beneficial actions of MSCs is the improvement of mitochondrial functions in the injured tissues by enhancing mitochondrial quality control (MQC). Recent advances in the understanding of cellular MQC, including mitochondrial biogenesis, mitophagy, fission, and fusion, helped uncover how MSCs enhance these processes. Specifically, MSCs have been suggested to regulate peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC1α)-dependent biogenesis, Parkin-dependent mitophagy, and Mitofusins (Mfn1/2) or Dynamin Related Protein-1 (Drp1)-mediated fission/fusion. In addition, previous studies also verified mitochondrial transfer from MSCs through tunneling nanotubes and via microvesicular transport. Combined, these effects improve mitochondrial functions, thereby contributing to the resolution of injury and inflammation. Thus, uncovering how MSCs affect MQC opens new therapeutic avenues for organ injury, and the transplantation of MSC-derived mitochondria to injured tissues might represent an attractive new therapeutic approach.

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Section: Mitochondrial Dysfunctionmentioning

confidence: 99%

Therapeutic Effects of Mesenchymal Stromal Cells Require Mitochondrial Transfer and Quality Control

Mukkala,

Jerkic,

Khan

et al. 2023

IJMS

View full text Add to dashboard Cite

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Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

Helmold,

Ahrens,

Fitzgerald

et al. 2024

Neural Regeneration Research

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Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease- causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein-protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration- approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

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Altered Metabolism in Motor Neuron Diseases: Mechanism and Potential Therapeutic Target

Cited by 2 publications

References 128 publications

Therapeutic Effects of Mesenchymal Stromal Cells Require Mitochondrial Transfer and Quality Control

Therapeutic Effects of Mesenchymal Stromal Cells Require Mitochondrial Transfer and Quality Control

Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

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