4 results match your criteria: "Leonard Miller School of Medicine of University of Miami[Affiliation]"
J Mol Med (Berl)
April 2022
Center for Orphan Drug Research, Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, 55455, USA.
Gaucher disease (GD), one of the most common lysosomal storage diseases, is caused by mutations in the gene, GBA1, that leads to defective glucocerebrosidase activity resulting in the accumulation and storage of glycosphingolipids. However, the pathophysiology of GD is more complicated leading to various associated conditions such as skeletal manifestations and Parkinson's disease (PD). These may result from oxidative stress and inflammatory responses due to complex interconnection of downstream factors such as substrate accumulation, endoplasmic reticulum (ER) stress, unfolded protein response (UPR), calcium dysregulation, mitochondrial dysfunction, defective autophagy, accumulation of α-synuclein aggregates, altered secretion and function of extracellular vesicles (EVs), and immunologic hyperactivity.
View Article and Find Full Text PDFMol Genet Metab Rep
December 2020
Department of Human Genetics and Medicine (Hematology), Leonard Miller School of Medicine of University of Miami, Miami, FL, United States.
Gaucher disease is an autosomal recessive metabolic disorder caused by mutations in , which encodes for the lysosomal hydrolase enzyme, β-glucocerebrosidase. The resulting misfolded protein can trigger endoplasmic reticulum stress and an unfolded protein response within the affected cells. The enzyme deficiency leads to accumulation of its substrates, glucosylceramide and glucosylsphingosine, within macrophage lysosomes and with prominent disease manifestations in macrophage rich tissues.
View Article and Find Full Text PDFMol Genet Metab
February 2020
Center for Orphan Drug Research, Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN 55455, United States of America. Electronic address:
The discovery that patients with Gaucher Disease (GD), a rare lysosomal storage disorder, were developing symptoms similar to Parkinson's disease (PD) led to investigation of the relationship between the two seemingly unrelated pathologies. GD, an autosomal recessive disorder, is the result of a biallelic mutation in the gene GBA1, which encodes for the enzyme glucocerebrosidase (GCase). Since the observation of its relation to PD, GBA1 mutations have become recognized as the most common genetic risk factor for development of synucleinopathies such as PD and dementia with Lewy bodies.
View Article and Find Full Text PDFJ Inherit Metab Dis
May 2020
Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota.
Type 1 Gaucher disease (GD1), a glycosphingolipid storage disorder caused by deficient activity of lysosomal glucocerebrosidase, is classically considered non-neuronopathic. However, current evidence challenges this view. Multiple studies show that mutations in GBA1 gene and decreased glucocerebrosidase activity are associated with increased risk for Parkinson disease.
View Article and Find Full Text PDF