The paper discusses one of the pigments of aging and pathological processes, including neu-rodegenerative ones - lipofuscin, as well as a model for its accelerated production and deg-radation methods. Original experiments on the effect of substances of different chemical na-ture on the formation of lipofuscin from rat liver mitochondria are presented.
Mitochondrial form and function are intricately linked through dynamic processes of fusion and fission, and disruptions in these processes are key drivers of neurodegenerative diseases, like Alzheimer’s. The inability of mitochondria to transition between their dynamic forms is a critical factor in the development of pathological states. In this paper, we focus on the importance of different types of mitochondrial phenotypes in nervous tissue, discussing how mitochondria in Alzheimer's disease are “stuck” in certain patterns and how this pattern maintains itself. Understanding the specific roles and transitions between mitochondrial forms, including tiny, networked, and hyperfused, is crucial in developing new therapies aimed at restoring mitochondrial homeostasis. By targeting these dynamics, we may be able to intervene early in the disease process, offering novel avenues for preventing or treating neurodegeneration.
This article discusses the age-related accumulation of hepatic lipofuscin in animals with a model of Alzheimer's disease. We present original experimental data showing a difference in the age-related accumulation of lipofuscin in the liver of 5xFAD mice and healthy mice.
In the article, the application of synaptosomes isolated from the brain as a means for mitochondrial delivery and restoration of mitobiogenesis for the therapy of Alzheimer's disease is discussed. Exper-imental data on the application of synaptosomes in mice with the 5XFAD model of Alzheimer's dis-ease are presented for the first time.
Background: Alzheimer's disease is a complex disease that begins long before the first well-known pathophysiological signs appear and requires, among other things, new diagnostic approaches. This is primarily due to the lack of effective treatment due to the lack of understanding of the disease mechanisms and the absence of correct biological models reflecting the cause-and-effect relationships in pathogenesis. One of the dysfunctional changes in AD is the disruption of mitochondrial fission and fusion processes. Methods: In this study, mitochondrial fusion and fission were regulated in primary neuro-astrocytic cultures of mouse hippocampus using mitochondrial fission inhibitor, mitochondrial fusion promoter and exogenous zinc. Changes in mitochondrial and cellular morphology were assessed, as well as lipofuscin levels as an early marker of mitochondrial dysfunction. Primary neuro-astrocytic hippocampal cultures of 5xFAD mice, representing a model of hereditary AD, were used for comparison. Results: Use of the mitochondrial fusion promoter converts the mitochondrial network to a pool of fused mitochondria and results in a drop in neuronal density by day 5 of exposure with a concomitant drop in astrocyte density by days 1 and 5 of exposure, accompanied by a drop in lipofuscin fluorescence intensity in culture. The use of mitochondrial fission inhibitor resulted in the appearance of fused mitochondria and disappearance of the pool of smallest mitochondria. This was accompanied by a decrease in neuronal density and an increase in astrocyte density with a concomitant increase in lipofuscin fluorescence intensity to the level of 5xFAD culture. Exogenous zinc induces mitochondrial fragmentation and at high concentrations leads to compensatory astrogliosis and neurodegeneration, while at low concentrations it decreases lipofuscin fluorescence intensity and affects culture morphology and changes in astrocyte immunoreactivity to GFAP. Conclusions: The study demonstrates that changing the processes of mitochondrial dynamics affects the morphology of adult cell cultures and can lead to processes similar to those observed in 5xFAD transgenic cultures. Keywords: Mitochondria, mitochondrial fusion and fission, 5xFAD, lipofuscin, Alzheimer's disease, primaryhippocampal culture
