4.6 Review

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

Related references

Note: Only part of the references are listed.
Article Clinical Neurology

Inhibiting mitochondrial fission rescues degeneration in hereditary spastic paraplegia neurons

Zhenyu Chen et al.

Summary: This study demonstrates that genetic or pharmacological inhibition of the mitochondrial fission mediator Drp1 can improve cytoskeletal organization and rescue axonal degeneration in patient-specific stem cell-derived cortical neurons of hereditary spastic paraplegias, providing potential therapeutic targets for these diseases.

BRAIN (2022)

Article Pharmacology & Pharmacy

Repurposing of Trimetazidine for amyotrophic lateral sclerosis: A study in SOD1(G93A) mice

Silvia Scaricamazza et al.

Summary: The therapeutic potential of the multi-target drug trimetazidine was evaluated in SOD1(G93A) mice. The results showed that trimetazidine delayed disease progression, improved motor function and metabolism, and increased overall survival of the mice.

BRITISH JOURNAL OF PHARMACOLOGY (2022)

Review Biochemistry & Molecular Biology

Hereditary Spastic Paraplegia: An Update

Arun Meyyazhagan et al.

Summary: This review provides an overview of hereditary spastic paraplegia (HSP), including its clinical manifestations, etiology, diagnosis, and treatment methods. Although modern medical interventions have helped, there is still room for improvement in the treatment of this disorder.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Article Neurosciences

Neuromuscular Junction Dysfunction in Amyotrophic Lateral Sclerosis

Sagar Verma et al.

Summary: Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by degeneration of motor neurons and potential early pathology at the neuromuscular junction (NMJ). However, the events triggering NMJ disassembly in ALS remain unclear.

MOLECULAR NEUROBIOLOGY (2022)

Article Biochemistry & Molecular Biology

TDP-43 Proteinopathy Causes Broad Metabolic Alterations including TCA Cycle Intermediates and Dopamine Levels in Drosophila Models of ALS

Suvithanandhini Loganathan et al.

Summary: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by motor neuron degeneration. This study investigated the metabolic changes induced by TDP-43, a protein associated with ALS, using a Drosophila ALS model. The results showed alterations in multiple metabolic pathways, including upregulation of Tricarboxylic acid (TCA) cycle metabolites and defects in neurotransmitter levels. Modulating TCA cycle flux and treatment with a dopamine agonist improved locomotor function in the ALS model.

METABOLITES (2022)

Article Clinical Neurology

Genetic origin of patients having spastic paraplegia with or without other neurologic manifestations

Jiannan Chen et al.

Summary: This study investigates the disease spectrum of hereditary spastic paraplegia (HSP) and identifies several other genetic neurological disorders characterized by spastic paraplegia. The study highlights the clinical, laboratorial, electrophysiological, and radiological features of these diseases, which can aid in differential diagnosis. Genetic testing plays a crucial role in providing a clear diagnosis and broadening the scope of testing can improve the rate of positive diagnosis.

BMC NEUROLOGY (2022)

Article Multidisciplinary Sciences

Mitochondrial dysregulation occurs early in ALS motor cortex with TDP-43 pathology and suggests maintaining NAD+ balance as a therapeutic strategy

Mukesh Gautam et al.

Summary: Mitochondrial defects lead to dysregulation of metabolomics and energy homeostasis in upper motor neurons (UMNs) with TDP-43 pathology. Reduced levels of NAD+ may be one of the underlying causes of these metabolomic problems. Our study shows that metabolomic defects occur early in ALS motor cortex and establishing NAD+ balance could offer therapeutic benefit to UMNs with TDP-43 pathology.

SCIENTIFIC REPORTS (2022)

Article Endocrinology & Metabolism

Neurons undergo pathogenic metabolic reprogramming in models of familial ALS

Sean-Patrick Riechers et al.

Summary: The study investigates the metabolism of neurons expressing familial ALS genes and finds that in rodent models of fALS, there is a rewiring of metabolism with reduced neuronal lactate production and maintained or enhanced activity of the neuronal citric acid cycle. This suggests that targeting fuel utilization adjustments in neurodegenerative diseases associated with mitochondrial dysfunction can be beneficial.

MOLECULAR METABOLISM (2022)

Article Multidisciplinary Sciences

Correlation of weight and body composition with disease progression rate in patients with amyotrophic lateral sclerosis

Jin-Yue Li et al.

Summary: This study aims to observe the nutritional status of Chinese patients with amyotrophic lateral sclerosis (ALS), and investigate its impact on disease progression. The results show that ALS patients have a significantly lower BMI, and weight loss is common along with muscle and fat wasting during the course of the disease. Body composition may serve as a prognostic factor and provide guidance for nutritional management in ALS patients.

SCIENTIFIC REPORTS (2022)

Article Neurosciences

Neuromuscular junction pathology is correlated with differential motor unit vulnerability in spinal and bulbar muscular atrophy

Elana Molotsky et al.

Summary: This study examines the relationship between neuromuscular junction (NMJ) pathology and vulnerability of fast-twitch motor units in spinal and bulbar muscular atrophy (SBMA) mouse models. The research reveals significantly increased NMJ and myofiber pathology in fast-twitch motor units, along with metabolic dysregulation and myofiber atrophy.

ACTA NEUROPATHOLOGICA COMMUNICATIONS (2022)

Review Biochemistry & Molecular Biology

Mitochondrial Dysfunction in Spinal Muscular Atrophy

Eleonora Zilio et al.

Summary: This review discusses the impact of spinal muscular atrophy (SMA) on mitochondrial functions in the neuronal and muscular systems, highlighting the potential contribution of mitochondrial defects to disease progression and the potential of restoring mitochondrial functionality as a therapeutic approach. The study also provides a list of transcripts encoding mitochondrial proteins affected in various SMA models and speculates that age-related mitochondrial deterioration may play a crucial role in adult SMA.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

Article Cell Biology

Autologous iPSC-Derived Human Neuromuscular Junction to Model the Pathophysiology of Hereditary Spastic Paraplegia

Domiziana Costamagna et al.

Summary: This study generated in vitro human neuromuscular junctions (NMJs) using a microfluidic strategy from patient-specific induced pluripotent stem cell (hiPSC) lines to model disease-relevant neuropathologic processes in hereditary spastic paraplegia (HSP). The unique strength of this NMJ model is its ability to generate lower motor neurons (MNs) and myotubes from autologous hiPSC origin while maintaining the genetic background of HSP patient donors. The study found that HSP-derived lines exhibited axonal swellings, reduced levels of SPASTIN protein, and impaired NMJ profiles, offering unique tools to study the pathologic mechanisms of HSP.

CELLS (2022)

Review Health Care Sciences & Services

Status of ALS Treatment, Insights into Therapeutic Challenges and Dilemmas

Mohammed Khamaysa et al.

Summary: This paper discusses the challenges in drug development for Amyotrophic lateral sclerosis (ALS) at the conceptual, technological, and methodological levels, as well as the socioeconomic and ethical issues related to the legitimate need of patients to benefit quickly from new treatments. It takes an optimistic view considering the recent approval of two new drugs in some countries and the development of targeted gene therapies.

JOURNAL OF PERSONALIZED MEDICINE (2022)

Article Biology

MND Phenotypes Differentiation: The Role of Multimodal Characterization at the Time of Diagnosis

Giuseppe Meo et al.

Summary: A multimodal characterization approach embedding clinical, cognitive/behavioral, genetic, and neurophysiological data can improve the differentiation of pUMN and pLMN from ALS at the time of diagnosis. Detailed clinical and neurophysiological examinations can significantly improve the differentiation of motor neuron diseases.

LIFE-BASEL (2022)

Review Biochemistry & Molecular Biology

CNS glucose metabolism in Amyotrophic Lateral Sclerosis: a therapeutic target?

Tesfaye Wolde Tefera et al.

Summary: ALS is a fatal progressive neurodegenerative disorder characterized by selective degeneration of motor neurons. There is evidence of abnormalities in energy metabolism, particularly in glucose metabolism, in ALS patients. Future investigations into modifying metabolic impairments to slow disease progression are crucial for understanding the disease and developing new therapeutic strategies.

CELL AND BIOSCIENCE (2021)

Article Clinical Neurology

Natural History of Pure Primary Lateral Sclerosis

Anhar Hassan et al.

Summary: The study showed that pure PLS patients did not convert to ALS after a median of 9 years of disease duration follow-up, with the ascending paraparetic phenotype being most common, presenting with early onset and frequent bladder symptoms. A minority of pure PLS patients develop a more pervasive neurodegenerative disorder after many years.

NEUROLOGY (2021)

Review Cell Biology

Skeletal Muscle in ALS: An Unappreciated Therapeutic Opportunity?

Silvia Scaricamazza et al.

Summary: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by motor neuron degeneration and muscle weakness. Despite efforts to target motor neurons, skeletal muscle alterations have been found to play a crucial role in the progression of the disease.

CELLS (2021)

Review Biochemistry & Molecular Biology

Insights into Clinical, Genetic, and Pathological Aspects of Hereditary Spastic Paraplegias: A Comprehensive Overview

Liena E. O. Elsayed et al.

Summary: Hereditary spastic paraplegias (HSP) are a heterogeneous group of motor neurodegenerative disorders characterized by a variety of clinical manifestations and modes of inheritance, posing challenges in diagnosis. Understanding the genetic and molecular pathways of HSP is crucial for the development of future biomarkers, predictors, and treatments.

FRONTIERS IN MOLECULAR BIOSCIENCES (2021)

Review Neurosciences

Hereditary Spastic Paraplegia and Future Therapeutic Directions: Beneficial Effects of Small Compounds Acting on Cellular Stress

Sentiljana Gumeni et al.

Summary: Hereditary spastic paraplegia (HSP) is a group of inherited neurodegenerative conditions characterized by degeneration of the longest axons within the corticospinal tract, leading to spasticity and weakness of the lower limbs. Current treatments include physiotherapy and muscle relaxant therapies, but more preclinical animal studies are needed to develop new treatment options.

FRONTIERS IN NEUROSCIENCE (2021)

Review Biochemistry & Molecular Biology

Mitochondrial Dysfunction Is a Common Denominator Linking Skeletal Muscle Wasting Due to Disease, Aging, and Prolonged Inactivity

Hayden W. Hyatt et al.

Summary: Skeletal muscle, essential for functions like breathing and movement, is susceptible to wasting due to various factors such as chronic diseases, cancer treatment, aging, and inactivity. Mitochondrial dysfunction plays a key role in this muscle wasting process, linking it to conditions like cancer, sepsis, and aging. Future research directions in this field are crucial for understanding and addressing muscle wasting.

ANTIOXIDANTS (2021)

Review Biochemistry & Molecular Biology

Skeletal Muscle Mitochondria Dysfunction in Genetic Neuromuscular Disorders with Cardiac Phenotype

Elena Ignatieva et al.

Summary: Mitochondrial dysfunction is considered the main cause of skeletal muscle wasting in various conditions, and genetically determined neuromuscular disorders often present with cardiac phenotypes. The specific roles of mitochondria in skeletal muscle under muscle-wasting conditions in cardiomyopathies have not been extensively studied.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Review Cell Biology

Skeletal Muscle Metabolism: Origin or Prognostic Factor for Amyotrophic Lateral Sclerosis (ALS) Development?

Cyril Quessada et al.

Summary: ALS is a fatal neurodegenerative disease characterized by progressive and selective loss of motor neurons, with metabolic changes playing a role in disease pathology. Correcting the loss of metabolic flexibility is now considered a major goal for ALS treatment.

CELLS (2021)

Article Biochemistry & Molecular Biology

ALS motor neurons exhibit hallmark metabolic defects that are rescued by SIRT3 activation

Jin-Hui Hor et al.

Summary: The study found that ALS patients' neurons exhibit a specific deficiency in mitochondrial respiration compared to healthy controls, which is attributed to hyper-acetylation of mitochondrial proteins. Activating the mitochondrial protein SIRT3 can reverse the metabolic defects in ALS neurons and correct a constellation of ALS-associated phenotypes.

CELL DEATH AND DIFFERENTIATION (2021)

Article Clinical Neurology

Primary lateral sclerosis: consensus diagnostic criteria

Martin R. Turner et al.

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY (2020)

Review Multidisciplinary Sciences

Mitochondrial TCA cycle metabolites control physiology and disease

Inmaculada Martinez-Reyes et al.

NATURE COMMUNICATIONS (2020)

Article Genetics & Heredity

The French national protocol for Kennedy's disease (SBMA): consensus diagnostic and management recommendations

Pierre-Francois Pradat et al.

ORPHANET JOURNAL OF RARE DISEASES (2020)

Review Clinical Neurology

Amyotrophic lateral sclerosis: a clinical review

P. Masrori et al.

EUROPEAN JOURNAL OF NEUROLOGY (2020)

Review Biochemistry & Molecular Biology

Mitochondrial electron transport chain: Oxidative phosphorylation, oxidant production, and methods of measurement

Deirdre Nolfi-Donegan et al.

REDOX BIOLOGY (2020)

Review Endocrinology & Metabolism

The Role of the Pentose Phosphate Pathway in Diabetes and Cancer

Tongxin Ge et al.

FRONTIERS IN ENDOCRINOLOGY (2020)

Review Medicine, General & Internal

New Treatments in Spinal Muscular Atrophy: Positive Results and New Challenges

Sonia Messina et al.

JOURNAL OF CLINICAL MEDICINE (2020)

Review Neurosciences

The TOR Pathway at the Neuromuscular Junction: More Than a Metabolic Player?

Perrine Castets et al.

FRONTIERS IN MOLECULAR NEUROSCIENCE (2020)

Review Neurosciences

The Neuromuscular Junction in Health and Disease: Molecular Mechanisms Governing Synaptic Formation and Homeostasis

Pedro M. Rodriguez Cruz et al.

FRONTIERS IN MOLECULAR NEUROSCIENCE (2020)

Review Clinical Neurology

Genetics of primary lateral sclerosis

Vincenzo Silani et al.

AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION (2020)

Review Endocrinology & Metabolism

Skeletal muscle energy metabolism during exercise

Mark Hargreaves et al.

NATURE METABOLISM (2020)

Review Neurosciences

The role of mitochondria in amyotrophic lateral sclerosis

Emma F. Smith et al.

NEUROSCIENCE LETTERS (2019)

Article Critical Care Medicine

Respiratory Failure in Amyotrophic Lateral Sclerosis

Shannon Niedermeyer et al.

CHEST (2019)

Review Physiology

Effect of Exercise on Fatty Acid Metabolism and Adipokine Secretion in Adipose Tissue

Adriana Mika et al.

FRONTIERS IN PHYSIOLOGY (2019)

Review Clinical Neurology

Epidemiology of amyotrophic lateral sclerosis: an update of recent literature

Elisa Longinetti et al.

CURRENT OPINION IN NEUROLOGY (2019)

Review Clinical Neurology

Ketone Bodies in Neurological Diseases: Focus on Neuroprotection and Underlying Mechanisms

Huajun Yang et al.

FRONTIERS IN NEUROLOGY (2019)

Article Multidisciplinary Sciences

Differentiation but not ALS mutations in FUS rewires motor neuron metabolism

Tijs Vandoorne et al.

NATURE COMMUNICATIONS (2019)

Review Neurosciences

ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now?

Rita Mejzini et al.

FRONTIERS IN NEUROSCIENCE (2019)

Review Clinical Neurology

Energy metabolism in ALS: an underappreciated opportunity?

Tijs Vandoorne et al.

ACTA NEUROPATHOLOGICA (2018)

Review Biochemistry & Molecular Biology

SOD1 in Amyotrophic Lateral Sclerosis: Ambivalent Behavior Connected to the Disease

Orietta Pansarasa et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2018)

Article Clinical Neurology

Hypermetabolism in ALS is associated with greater functional decline and shorter survival

Frederik J. Steyn et al.

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY (2018)

Review Clinical Neurology

Biomarkers of Spinal and Bulbar Muscle Atrophy (SBMA): A Comprehensive Review

Giorgia Querin et al.

FRONTIERS IN NEUROLOGY (2018)

Article Medicine, General & Internal

X-linked spinal and bulbar muscular atrophy (Kennedy's disease): the first case described in the Brazilian Amazon

Camila Nascimento Alves et al.

EINSTEIN-SAO PAULO (2018)

Review Physiology

Causes and consequences of age-related changes at the neuromuscular junction

Daniel J. Ham et al.

CURRENT OPINION IN PHYSIOLOGY (2018)

Review Clinical Neurology

Gene discovery in amyotrophic lateral sclerosis: implications for clinical management

Ammar Al-Chalabi et al.

NATURE REVIEWS NEUROLOGY (2017)

Review Cell Biology

What is Hyper in the ALS Hypermetabolism?

Alberto Ferri et al.

MEDIATORS OF INFLAMMATION (2017)

Review Behavioral Sciences

The neuropathological signature of bulbar-onset ALS: A systematic review

S. Shellikeri et al.

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS (2017)

Article Genetics & Heredity

Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy a literature review

Ingrid E. C. Verhaart et al.

ORPHANET JOURNAL OF RARE DISEASES (2017)

Review Clinical Neurology

Mitochondrial implications in bulbospinal muscular atrophy (Kennedy disease)

Josef Finsterer et al.

AMYOTROPHIC LATERAL SCLEROSIS AND FRONTOTEMPORAL DEGENERATION (2016)

Article Biochemistry & Molecular Biology

Motor neuron mitochondrial dysfunction in spinal muscular atrophy

Nimrod Miller et al.

HUMAN MOLECULAR GENETICS (2016)

Article Clinical Neurology

Mitochondrial dysfunction in hereditary spastic paraparesis with mutations in DDHD1/SPG28

Andrea Mignarri et al.

JOURNAL OF THE NEUROLOGICAL SCIENCES (2016)

Review Multidisciplinary Sciences

Decoding ALS: from genes to mechanism

J. Paul Taylor et al.

NATURE (2016)

Review Anatomy & Morphology

Neuromuscular Junctions as Key Contributors and Therapeutic Targets in Spinal Muscular Atrophy

Marina Boido et al.

FRONTIERS IN NEUROANATOMY (2016)

Review Clinical Neurology

Dissociated lower limb muscle involvement in amyotrophic lateral sclerosis

Neil G. Simon et al.

JOURNAL OF NEUROLOGY (2015)

Article Clinical Neurology

Primary Lateral Sclerosis

Jeffrey M. Statland et al.

NEUROLOGIC CLINICS (2015)

Article Clinical Neurology

Spinal Muscular Atrophy

Stephen J. Kolb et al.

NEUROLOGIC CLINICS (2015)

Review Clinical Neurology

SOD1 Function and Its Implications for Amyotrophic Lateral Sclerosis Pathology: New and Renascent Themes

Rosie K. A. Bunton-Stasyshyn et al.

NEUROSCIENTIST (2015)

Review Pharmacology & Pharmacy

Mitochondrial dysfunction in amyotrophic lateral sclerosis - a valid pharmacological target?

H. Muyderman et al.

BRITISH JOURNAL OF PHARMACOLOGY (2014)

Article Clinical Neurology

Functional pattern of brain FDG-PET in amyotrophic lateral sclerosis

Marco Pagani et al.

NEUROLOGY (2014)

Article Cell Biology

Interaction between AP-5 and the hereditary spastic paraplegia proteins SPG11 and SPG15

Jennifer Hirst et al.

MOLECULAR BIOLOGY OF THE CELL (2013)

Review Physiology

EXERCISE, GLUT4, AND SKELETAL MUSCLE GLUCOSE UPTAKE

Erik A. Richter et al.

PHYSIOLOGICAL REVIEWS (2013)

Review Neurosciences

Sugar for the brain: the role of glucose in physiological and pathological brain function

Philipp Mergenthaler et al.

TRENDS IN NEUROSCIENCES (2013)

Article Genetics & Heredity

Alteration of Fatty-Acid-Metabolizing Enzymes Affects Mitochondrial Form and Function in Hereditary Spastic Paraplegia

Christelle Tesson et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2012)

Article Clinical Neurology

Loss of ERLIN2 Function Leads to Juvenile Primary Lateral Sclerosis

Amr Al-Saif et al.

ANNALS OF NEUROLOGY (2012)

Review Neurosciences

Current Status of Treatment of Spinal and Bulbar Muscular Atrophy

Fumiaki Tanaka et al.

NEURAL PLASTICITY (2012)

Article Biochemistry & Molecular Biology

ALS-associated fused in sarcoma (FUS) mutations disrupt Transportin-mediated nuclear import

Dorothee Dormann et al.

EMBO JOURNAL (2010)

Article Medicine, General & Internal

Effects of Gender in Amyotrophic Lateral Sclerosis

Pamela A. McCombe et al.

GENDER MEDICINE (2010)

Article Multidisciplinary Sciences

Regional aerobic glycolysis in the human brain

S. Neil Vaishnavi et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2010)

Article Clinical Neurology

High metabolic level in patients with familial amyotrophic lateral sclerosis

Benoit Funalot et al.

AMYOTROPHIC LATERAL SCLEROSIS (2009)

Review Clinical Neurology

Prognostic factors in ALS: A critical review

Adriano Chio et al.

AMYOTROPHIC LATERAL SCLEROSIS (2009)

Review Medicine, General & Internal

Spinal muscular atrophy

Mitchell R. Lunn et al.

LANCET (2008)

Article Clinical Neurology

Spinal muscular atrophy: Clinical classification and disease heterogeneity

Barry S. Russman

JOURNAL OF CHILD NEUROLOGY (2007)

Article Clinical Neurology

Mitochondrial alterations in the spinal cord of patients with sporadic amyotrophic lateral sclerosis

Shoichi Sasaki et al.

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY (2007)

Review Clinical Neurology

Primary lateral sclerosis

Mike A. Singer et al.

MUSCLE & NERVE (2007)

Article Multidisciplinary Sciences

Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis

Manuela Neumann et al.

SCIENCE (2006)

Article Biochemistry & Molecular Biology

Mutated human SOD1 causes dysfunction of oxidative phosphorylation in mitochondria of transgenic mice

M Mattiazzi et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2002)

Article Clinical Neurology

Detection of preclinical motor neurone loss in SOD1 mutation carriers using motor unit number estimation

A Aggarwal et al.

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY (2002)

Article Biochemistry & Molecular Biology

Mitochondrial DNA and respiratory chain function in spinal cords of ALS patients

FR Wiedemann et al.

JOURNAL OF NEUROCHEMISTRY (2002)

Article Clinical Neurology

Primary lateral sclerosis: clinical, neurophysiological, and magnetic resonance findings

J Kuipers-Upmeijer et al.

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY (2001)

Article Neurosciences

Mitochondrial DNA deletion mutation levels are elevated in ALS brains

GK Dhaliwal et al.

NEUROREPORT (2000)

Review Clinical Neurology

Hereditary spastic paraparesis: a review of new developments

CJ McDermott et al.

JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY (2000)