Defects in calcium homeostasis and mitochondria can be reversed in Pompe disease

Lim, Jeong‐A; Li, Lishu; Kakhlon, Or; Myerowitz, Rachel; Raben, Nina

doi:10.1080/15548627.2015.1009779

Cited by 95 publications

(110 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Lim et al recently showed that mitochondrial oxidative stress induces the skeletal muscle pathology of PD and that Ca 2+ homeostasis is dysregulated in the skeletal muscle of PD mice . The link between mitochondrial stress and oxidative stress is more clearly demonstrated by the results presented in this study.…”

Section: Discussionsupporting

confidence: 72%

Metabolomic Profiling of Pompe Disease-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Reveals That Oxidative Stress Is Associated with Cardiac and Skeletal Muscle Pathology

Sato

Kobayashi

Higuchi

et al. 2016

Stem Cells Translational Medicine

View full text Add to dashboard Cite

Pompe disease (PD) is a lysosomal storage disease that is caused by a deficiency of the acid α‐glucosidase, which results in glycogen accumulation in the lysosome. The major clinical symptoms of PD include skeletal muscle weakness, respiratory failure, and cardiac hypertrophy. Based on its severity and symptom onset, PD is classified into infantile and late‐onset forms. Lysosomal accumulation of glycogen can promote many types of cellular dysfunction, such as autophagic dysfunction, endoplasmic reticulum stress, and abnormal calcium signaling within skeletal muscle. However, the disease mechanism underlying PD cardiomyopathy is not fully understood. Several researchers have shown that PD induced pluripotent stem cell (iPSC)‐derived cardiomyocytes successfully replicate the disease phenotype and are useful disease models. We have analyzed the metabolomic profile of late‐onset PD iPSC‐derived cardiomyocytes and found that oxidative stress and mitochondrial dysfunction are likely associated with cardiac complications. Furthermore, we have validated that these disease‐specific changes were also observed in the cardiomyocytes and skeletal muscle of a genetically engineered murine PD model. Oxidative stress may contribute to skeletal muscle and cardiomyocyte dysfunction in PD mice; however, NF‐E2‐related factor 2 was downregulated in cardiomyocytes and skeletal muscle, despite evidence of oxidative stress. We hypothesized that oxidative stress and an impaired antioxidative stress response mechanism may underlie the molecular pathology of late‐onset PD. Stem Cells Translational Medicine 2017;6:31–39

show abstract

Section: Discussionsupporting

confidence: 72%

Metabolomic Profiling of Pompe Disease-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Reveals That Oxidative Stress Is Associated with Cardiac and Skeletal Muscle Pathology

Sato

Kobayashi

Higuchi

et al. 2016

Stem Cells Translational Medicine

View full text Add to dashboard Cite

show abstract

“…We therefore recommend a thorough multi-dimensional approach to allow for early identification of typical and subtle features of patients with “late-onset” GAA variants [37 38 42]. Evaluation by a pediatric physical therapist with expertise in neuromuscular disorders is critical for an age appropriate assessment of muscular weakness, as it may not be appreciable on medical clinical examination alone.…”

Section: Discussionmentioning

confidence: 99%

Insight into the phenotype of infants with Pompe disease identified by newborn screening with the common c.-32-13T > G “late-onset” GAA variant

Rairikar

Case

Bailey

et al. 2017

Molecular Genetics and Metabolism

View full text Add to dashboard Cite

Objective Newborn screening (NBS) has led to early diagnosis and early initiation of treatment for infantile onset Pompe Disease (IOPD). However, guidelines for management of late onset Pompe disease (LOPD) via NBS, especially with the IVS c.-32-13T>G are not clear. This IVS variant is noted in 68–90% cases with LOPD and has been presumed to result in “adult” disease in compound heterozygosity, with a few cases with earlier onset and a mild to no phenotype in homozygosity. Our study evaluates newborns with LOPD having IVS variant with a diligent multidisciplinary approach to determine if they have an early presentation. Methods Seven children with LOPD identified by NBS with IVS variant (3 compound heterozygous, and 4 homozygous) were evaluated with clinical, biochemical (CK, AST, ALT, and urinary Glc4), cardiac evaluation, physical therapy (PT), occupational, and speech/language therapy. Results All seven patients demonstrated motor involvement by age 6 months; the three patients with c.-32-13 T>G variant in compound heterozygosity had symptoms as neonates. Patients with c.-32-13 T>G variant in compound heterozygosity had more involvement with persistent hyperCKemia, elevated AST and ALT, swallowing difficulties, limb-girdle weakness, delayed motor milestones, and were initiated on ERT. The patients with c.-32-13T>G variant in homozygosity had normal laboratory parameters, and presented with very subtle yet LOPD specific signs, identified only by meticulous assessments. Conclusion This patient cohort represents the first carefully phenotyped cohort of infants with LOPD with the “late-onset” GAA variant c.-32-13T>G detected by NBS in the USA. It emphasizes not only the opportunity for early detection of skeletal and other muscle involvement in infants with c.-32-13T>G variant but also a high probability of overlooking or underestimating the significance of clinically present and detectable features. It can thus serve as a valuable contribution in the development of evaluation and treatment algorithms for infants with LOPD.

show abstract

“…Известно, что N-концевой α-сегмент действует в качестве сен-сора разности потенциалов и регулирует ток ионов и диффузию метаболитов. VDAC1 позволяет ионам Ca 2+ проникать через наружную мембрану с высокой скоростью, что приводит к увеличению уровня ионов в митохондриях [18,23].…”

Section: термодинамикаunclassified

“…Помимо апоптоза, кльциевые сигналы играют важ-ную роль в регуляции аутофагии [23,29]. Активация этого процесса осуществляется в условиях блокады унипорта и ингибирования ионозитол-чувствитель-ных рецепторов.…”

Section: роль митохондрий в апоптозе лимфоцитовunclassified

The Role of Mitochondria in the Regulation of Lymphocyte Calcium Signaling

Lychkovskaya¹,

Trufanofa²,

Semenchukov³

et al. 2016

SMR

View full text Add to dashboard Cite

Defects in calcium homeostasis and mitochondria can be reversed in Pompe disease

Cited by 95 publications

References 96 publications

Metabolomic Profiling of Pompe Disease-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Reveals That Oxidative Stress Is Associated with Cardiac and Skeletal Muscle Pathology

Metabolomic Profiling of Pompe Disease-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Reveals That Oxidative Stress Is Associated with Cardiac and Skeletal Muscle Pathology

Insight into the phenotype of infants with Pompe disease identified by newborn screening with the common c.-32-13T > G “late-onset” GAA variant

The Role of Mitochondria in the Regulation of Lymphocyte Calcium Signaling

Contact Info

Product

Resources

About