Abstract
The concept of lysosomotropic agents significantly changed numerous aspects of cellular biochemistry, biochemical pharmacology, and clinical medicine. In the present review, we focused on numerous low-molecular and high-molecular lipophilic basic compounds and on the role of lipophagy and autophagy in experimental and clinical medicine. Attention was primarily focused on the most promising agents acting as autophagy inducers, which offer a new window for treatment and/or prophylaxis of various diseases, including type 2 diabetes mellitus, Parkinson’s disease, and atherosclerosis. The present review summarizes current knowledge on the lysosomotropic features of medical drugs, as well as autophagy inducers, and their role in pathological processes.
Highlights
The concept of lysosomotropic agents (LA) was introduced by de Duve and coauthors soon after their discovery of a new class of subcellular organelles: lysosomes
Using this well-documented mouse model of hyperlipidemia, it has been previously established that a single dose (300 mg/kg) of poloxamer 407 (P-407) induces a significant increase in serum total cholesterol, LDL-C, and especially TG, at 24 h post-dosing when compared to saline-treated controls (Figure 1A–C), and that the hyperlipidemic state persists for approximately 5 days post-dosing, TG returns to baseline levels by three days following P-407 treatment (Figure 1C)
It has been reported that an uncharacterized transcriptional component of TH-dependent autophagy-lysosome induction in macrophages is associated with increased levels and nuclear translocation of TFEB, which is an activator of a broad network of autophagic and lysosomal genes [16]
Summary
The concept of lysosomotropic agents (LA) was introduced by de Duve and coauthors soon after their discovery of a new class of subcellular organelles: lysosomes This concept has had a great influence on the development of cellular biochemistry, biochemical pharmacology, and clinical medicine. Many drugs in clinical practice are characterized by special effects on the cell, including vacuolization, changes in lysosomal-membrane permeability, an increased number and size of lysosomes, and, in some cases, accumulation of undegraded material. These molecules have significant therapeutic activity and are used in clinical practice for treatment of several psychoses, malaria, and depression (for review, see Kuzu et al [4]).
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