The change in activity of lysosomal hydrolases in the brain tissue of patients with demyelinating disease has been suggested to reflect the demyelination process. In this study we measured neutral proteinase (NP), acid proteinase (AP), and beta-glucuronidase (BG) activities in CSF of 32 patients with multiple sclerosis (MS) (remitting, remitting and relapsing, or chronic progressive course of the disease), 62 controls, and 4 patients with chronic inflammatory disease of central nervous system (ID). Samples from MS patients were taken at different clinical conditions of the disease during the 22-month follow-up. Elevated NP activity was found in patients with relapsing course of MS and also in patients with ID (P less than 0.05). NP activity correlated with the number of leucocytes in CSF of both MS (P less than 0.005, r = 0.50) and control (P less than 0.05, r = 0.21) patients. AP activity decreased in the MS group, especially in patients with remitting or remitting and relapsing courses of the disease (P less than 0.05), but even more in patients with ID (P less than 0.01). During the follow-up the increase in NP activity seemed to be associated with the clinical relapses of MS patients. Other enzymes did not fluctuate with the disease. This study suggests that the change in activity of lysosomal hydrolases is not specific for MS. The increase in NP activity in CSF is associated with clinical relapse of individual MS patients during the follow-up and may indicate immunological activation of the demyelination process in the brain. The large intra- and interindividual variation in enzyme activities in the CSF, however, makes the use of these enzymes difficult for diagnosis of MS and follow-up of MS activity.
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http://dx.doi.org/10.1016/0022-510x(87)90234-6 | DOI Listing |
Autophagy
January 2025
School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Glia contribute to the neuropathology of Parkinson disease (PD), but how they react opposingly to be beneficial or detrimental under pathological conditions, like promoting or eliminating SNCA/α-syn (synuclein alpha) inclusions, remains elusive. Here we present evidence that aux (auxilin), the homolog of the PD risk factor GAK (cyclin G associated kinase), regulates the lysosomal degradation of SNCA/α-syn in glia. Lack of glial GAK/aux increases the lysosome number and size, regulates lysosomal acidification and hydrolase activity, and ultimately blocks the degradation of substrates including SNCA/α-syn.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), 90146 Palermo, Italy.
Pompe disease is a neuromuscular disorder caused by a deficiency of the enzyme acid alpha-glucosidase (), which leads to lysosomal glycogen accumulation and progressive development of muscle weakness. Two distinct isoforms have been identified. In the infantile form, the weakness is often severe and leads to motor difficulties from the first few months of life.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Experimental Medicine, University of Salento, Via Provinciale Lecce-Monteroni n. 165, 73100 Lecce, Italy.
Peripherin belongs to heterogeneous class III of intermediate filaments, and it is the only intermediate filament protein selectively expressed in the neurons of the peripheral nervous system. It has been previously discovered that peripherin interacts with proteins important for the endo-lysosomal system and for the transport to late endosomes and lysosomes, such as RAB7A and AP-3, although little is known about its role in the endocytic pathway. Here, we show that peripherin silencing affects lysosomal abundance but also positioning, causing the redistribution of lysosomes from the perinuclear area to the cell periphery.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), 90146 Palermo, Italy.
Anderson-Fabry disease is a hereditary, progressive, multisystemic lysosomal storage disorder caused by a functional deficiency of the enzyme α-galactosidase A (α-GalA). This defect is due to mutations in the gene, located in the long arm of the X chromosome (Xq21-22). Functional deficiency of the α-GalA enzyme leads to reduced degradation and accumulation of its substrates, predominantly globotriaosylceramide (Gb3), which accumulate in the lysosomes of numerous cell types, giving rise to the symptomatology.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), 90146 Palermo, Italy.
Anderson-Fabry (or Fabry) disease is a rare lysosomal storage disorder caused by a functional deficiency of the enzyme alpha-galactosidase A. The partial or total defect of this lysosomal enzyme, which is caused by variants in the gene, leads to the accumulation of glycosphingolipids, mainly globotriaosylceramide in the lysosomes of different cell types. The clinical presentation of Fabry disease is multisystemic and can vary depending on the specific genetic variants associated with the disease.
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