Lysosomal storage diseases (LSDs) are a group of approximately 50 genetic disorders caused by mutations in genes coding enzymes that are involved in cell degradation and transferring lipids and other macromolecules. Accumulation of lipids and other macromolecules in lysosomes leads to the destruction of affected cells. Although the clinical manifestations of different LSDs vary greatly, more than half of LSDs have symptoms of central nervous system neurodegeneration, and within each disorder there is a considerable variation, ranging from severe, infantile-onset forms to attenuated adult-onset disease, sometimes with distinct clinical features. To date, treatment options for this group of diseases remain limited, which highlights the need for further development of innovative therapeutic approaches, that can not only improve the patients’ quality of life, but also provide full recovery for them. In many LSDs stem cell-based therapy showed promising results in preclinical researches. This review discusses using mesenchymal stem cells for different LSDs therapy and other neurodegenerative diseases and their possible limitations.
Despite extensive research on neurological disorders, unanswered questions remain regarding the molecular mechanisms underpinning the course of these diseases, and the search continues for effective biomarkers for early diagnosis, prognosis, or therapeutic intervention. These questions are especially acute in the study of spinal cord injury (SCI) and neurodegenerative diseases. It is believed that the changes in gene expression associated with processes triggered by neurological disorders are the result of post-transcriptional gene regulation. microRNAs (miRNAs) are key regulators of post-transcriptional gene expression and, as such, are often looked to in the search for effective biomarkers. We propose that cerebrospinal fluid (CSF) is potentially a source of biomarkers since it is in direct contact with the central nervous system and therefore may contain biomarkers indicating neurodegeneration or damage to the brain and spinal cord. However, since the abundance of miRNAs in CSF is low, their isolation and detection is technically difficult. In this review, we evaluate the findings of recent studies of CSF miRNAs as biomarkers of spinal cord injury (SCI) and neurodegenerative diseases. We also summarize the current knowledge concerning the methods of studying miRNA in CSF, including RNA isolation and normalization of the data, highlighting the caveats of these approaches and possible solutions.
Immunohistochemical study with monoclonal antibodies against fast myosin heavy chains showed that excision of a fragment of sciatic nerve does not change, while compression of the nerve decreased the relative content of fast muscle fibers in rat soleus muscle. The content of fast fibers in the muscles of contralateral limbs decreased in both models of denervation. Hence, contralateral limbs cannot be used as the control in experiments with disturbed neurotrophic function. Possible mechanisms underlying changes in the immunohistochemical profiles of experimental and contralateral limbs are discussed.
The use of monoclonal antibodies to the heavy cbains of fast myosin shows that twicerepeated sensitization (ovalburnin + aluminum hydroxide gel) elicits different effects in the muscles examined, raising the content of the fast muscle fibers in m. frenicus and of the slow muscle fibers in m. plantaris. Changes in the irnmunohistochemical profile do not entirely correlate with changes in the contractile characteristics.Key Words: fast and slow muscle; sensitization; immunohistochemistry; myosins; contractile characteristics Humoral regulation of the function of skeletal muscle remains one of the least studied problems. Whereas the effect of some hormones on the morphofunctional characteristics of skeletal muscle has been thoroughly investigated [4,13], the role of other humoral factors in the regulation of skeletal muscle phenotypes has been neglected. It is not yet certain what effect sensitization has on different parameters of skeletal muscle [3,9], although the skeletal muscle tissue could hardly remain insensitive to allergic processes in the organism. The importance of studies of allergic reactions in skeletal muscle is primarily determined by clinical demands. Diverse disturbances of the external respiration, which may derive from altered functions of the diaphragmal and intercostal muscles, due to allergic reaction, are among the factors underlying the pathogenesis of bronchial asthma [5]. The slow and fast muscles of mammals have been shown to differ with respect to their plasticity and may respond differently to the same factors [2,10,11]. We previously demonstrated, using histochemical methods, that sensitization does not alter the The aim of the present study was to investigate the qualitative composition of myosin and the contractile characteristics of the slow and fast skeletal muscle of guinea pig under conditions of protein-induced sensitization. MATERIALS AND METHODSThe experiments were carried out on the fast (m. plantaris) and slow (m. frenicus) muscles of adult male guinea pigs weighing 350-400 g. Twice-repeated sensitization was performed by subcutaneous injections in the thigh of a solution containing 10 lag ovalbumin and 1 mg dry aluminum hydroxide gel in 1 ml of physiological saline per animal. The second injection was performed 14 days after the first. The level of sensitization was monitored by the methods of passive skin anaphylaxis [7] and thin-layer immune assay [8]; on day 21 the antibody (AB) titer constituted 1/256-1/1024 and 1/ 25-1/512, respectively. The muscles were examined 3 weeks after the start of experiments. Animals were decapitated under deep ether anesthesia, the muscles were excised, and cryostate sections 8 I.t
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