scholarly journals Mitochondrial Dysfunction and Neurodegeneration in Lysosomal Storage Disorders

2017 ◽  
Vol 23 (2) ◽  
pp. 116-134 ◽  
Author(s):  
Nicoletta Plotegher ◽  
Michael R. Duchen
Keyword(s):  
Mitochondrial Dysfunction ◽  
Lysosomal Storage Disorders ◽  
Lysosomal Storage ◽  
Storage Disorders

scholarly journals Mitochondrial Dysfunction in Lysosomal Storage Disorders

Diseases ◽  
2016 ◽  
Vol 4 (4) ◽  
pp. 31 ◽  
Author(s):  
Mario de la Mata ◽  
David Cotán ◽  
Marina Villanueva-Paz ◽  
Isabel de Lavera ◽  
Mónica Álvarez-Córdoba ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Lysosomal Storage Disorders ◽  
Lysosomal Storage ◽  
Storage Disorders

scholarly journals Mechanisms of Mitochondrial Dysfunction in Lysosomal Storage Disorders: A Review

2020 ◽  
Vol 9 (8) ◽  
pp. 2596
Author(s):  
Karolina M. Stepien ◽  
Federico Roncaroli ◽  
Nadia Turton ◽  
Christian J. Hendriksz ◽  
Mark Roberts ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Clinical Information ◽  
Lysosomal Storage Disorders ◽  
Contributory Factor ◽  
Symbiotic Relationship ◽  
Oxygen Species ◽  
Lysosomal Storage ◽  
Inhibitory Mechanisms ◽  
And Oxidative Stress ◽  
Storage Disorders

Mitochondrial dysfunction is emerging as an important contributory factor to the pathophysiology of lysosomal storage disorders (LSDs). The cause of mitochondrial dysfunction in LSDs appears to be multifactorial, although impaired mitophagy and oxidative stress appear to be common inhibitory mechanisms shared amongst these heterogeneous disorders. Once impaired, dysfunctional mitochondria may impact upon the function of the lysosome by the generation of reactive oxygen species as well as depriving the lysosome of ATP which is required by the V-ATPase proton pump to maintain the acidity of the lumen. Given the reported evidence of mitochondrial dysfunction in LSDs together with the important symbiotic relationship between these two organelles, therapeutic strategies targeting both lysosome and mitochondrial dysfunction may be an important consideration in the treatment of LSDs. In this review we examine the putative mechanisms that may be responsible for mitochondrial dysfunction in reported LSDs which will be supplemented with morphological and clinical information.

scholarly journals Potential resistance to SARS-CoV-2 infection in lysosomal storage disorders

2021 ◽  
Author(s):  
Maurizio Pieroni ◽  
Federico Pieruzzi ◽  
Renzo Mignani ◽  
Francesca Graziani ◽  
Iacopo Olivotto ◽  
...  
Keyword(s):  
Lysosomal Storage Disorders ◽  
Lysosomal Storage ◽  
Storage Disorders

scholarly journals Altered heparan sulfate metabolism during development triggers dopamine-dependent autistic-behaviours in models of lysosomal storage disorders

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Maria De Risi ◽  
Michele Tufano ◽  
Filomena Grazia Alvino ◽  
Maria Grazia Ferraro ◽  
Giulia Torromino ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Sch 23390 ◽  
Lysosomal Storage Disorders ◽  
Dopamine Neurons ◽  
Therapeutic Effects ◽  
Lysosomal Storage ◽  
Cellular Models ◽  
Mps Ii ◽  
Mps Iiia ◽  
Storage Disorders

AbstractLysosomal storage disorders characterized by altered metabolism of heparan sulfate, including Mucopolysaccharidosis (MPS) III and MPS-II, exhibit lysosomal dysfunctions leading to neurodegeneration and dementia in children. In lysosomal storage disorders, dementia is preceded by severe and therapy-resistant autistic-like symptoms of unknown cause. Using mouse and cellular models of MPS-IIIA, we discovered that autistic-like behaviours are due to increased proliferation of mesencephalic dopamine neurons originating during embryogenesis, which is not due to lysosomal dysfunction, but to altered HS function. Hyperdopaminergia and autistic-like behaviours are corrected by the dopamine D1-like receptor antagonist SCH-23390, providing a potential alternative strategy to the D2-like antagonist haloperidol that has only minimal therapeutic effects in MPS-IIIA. These findings identify embryonic dopaminergic neurodevelopmental defects due to altered function of HS leading to autistic-like behaviours in MPS-II and MPS-IIIA and support evidence showing that altered HS-related gene function is causative of autism.

Lysosomal Storage Disorders as an Etiology of Nonimmune Hydrops Fetalis: A Systematic Review

2021 ◽  
Author(s):  
Neel S. Iyer ◽  
Alexis C. Gimovsky ◽  
Carlos R. Ferreira ◽  
Elizabeth J. Critchlow ◽  
Huda B. Al‐kouatly
Keyword(s):  
Systematic Review ◽  
Lysosomal Storage Disorders ◽  
Hydrops Fetalis ◽  
Lysosomal Storage ◽  
Nonimmune Hydrops ◽  
Storage Disorders

scholarly journals A charitable access program for patients with lysosomal storage disorders in underserved communities worldwide

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Atul Mehta ◽  
Uma Ramaswami ◽  
Joseph Muenzer ◽  
Roberto Giugliani ◽  
Kurt Ullrich ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Clinical Manifestations ◽  
Lysosomal Storage Disorders ◽  
Expert Committee ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Mps Ii ◽  
Access Program ◽  
Storage Disorders

Abstract Background Lysosomal storage disorders (LSDs) are rare genetic disorders, with heterogeneous clinical manifestations and severity. Treatment options, such as enzyme replacement therapy (ERT), substrate replacement therapy, and pharmacological chaperone therapy, are available for several LSDs, including Gaucher disease (GD), Fabry disease (FD), and Hunter syndrome (mucopolysaccharidosis type II [MPS II]). However, patients in some countries face challenges accessing treatments owing to limited availability of locally licensed, approved drugs. Methods The Takeda LSD Charitable access program aims to meet the needs of individuals with GD, FD or MPS II with the greatest overall likelihood of benefit, in selected countries, through donation of ERT to nonprofit organizations, and support for medical capacity-building as well as family support via independent grants. Long-term aims of the program are to establish sustainable healthcare services delivered by local healthcare providers for patients with rare metabolic diseases. Patients receiving treatment through the program are monitored regularly, and their clinical data and progress are reviewed annually by an independent medical expert committee (MEC). The MEC also selects patients for enrollment completely independent from the sponsoring company. Results As of 31 August, 2019, 199 patients from 13 countries were enrolled in the program; 142 with GD, 41 with MPS II, and 16 with FD. Physicians reported improvements in clinical condition for 147 (95%) of 155 patients with follow-up data at 1 year. Conclusions The response rate for follow-up data at 1 year was high, with data collected for > 90% of patients who received ERT through the program showing clinical improvements in the majority of patients. These findings suggest that the program can benefit selected patients previously unable to access disease-specific treatments. Further innovative solutions and efforts are needed to address the challenges and unmet needs of patients with LSDs and other rare diseases around the world.

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