Assessing the contribution of the chemical exposome to neurodegenerative disease

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(5), P. 812 - 821

Published: April 29, 2024

Language: Английский

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Modeling the neuroimmune system in Alzheimer’s and Parkinson’s diseases

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Jan. 23, 2024

Abstract Parkinson’s disease (PD) and Alzheimer’s (AD) are neurodegenerative disorders caused by the interaction of genetic, environmental, familial factors. These diseases have distinct pathologies symptoms that linked to specific cell populations in brain. Notably, immune system has been implicated both diseases, with a particular focus on dysfunction microglia, brain’s resident cells, contributing neuronal loss exacerbating symptoms. Researchers use models neuroimmune gain deeper understanding physiological biological aspects these how they progress. Several vitro vivo models, including 2D cultures animal utilized. Recently, advancements made optimizing existing developing 3D organ-on-a-chip systems, holding tremendous promise accurately mimicking intricate intracellular environment. As result, represent crucial breakthrough transformation current treatments for PD AD offering potential conducting long-term disease-based modeling therapeutic testing, reducing reliance significantly improving viability compared conventional models. The application research marks prosperous step forward, providing more realistic representation complex interactions within system. Ultimately, refined aim aid quest combat mitigate impact debilitating patients their families.

Language: Английский

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CD38 in Neurodegeneration and Neuroinflammation

Cells, Journal Year: 2020, Volume and Issue: 9(2), P. 471 - 471

Published: Feb. 18, 2020

Neurodegenerative diseases are characterized by neuronal degeneration as well neuroinflammation. While CD38 is strongly expressed in brain cells including neurons, astrocytes microglial cells, the role played neurodegeneration and neuroinflammation remains elusive. Yet, expression increases a consequence of aging which otherwise primary risk associated with neurodegenerative diseases, several experimental data demonstrated that knockout mice protected from neuroinflammatory insults. Moreover, nicotinamide adenine dinucleotide, whose levels tightly controlled CD38, recognized potent neuroprotective agent, NAD supplementation was found to be beneficial against diseases. The aims this review summarize physiological brain, present arguments indicating involvement neuroinflammation, discuss these observations light complex biology.

Language: Английский

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Cellular Mechanisms of Melatonin: Insight from Neurodegenerative Diseases

Biomolecules, Journal Year: 2020, Volume and Issue: 10(8), P. 1158 - 1158

Published: Aug. 7, 2020

Neurodegenerative diseases are the second most common cause of death and characterized by progressive impairments in movement or mental functioning central peripheral nervous system. The prevention neurodegenerative disorders has become an emerging public health challenge for our society. Melatonin, a pineal hormone, various physiological functions brain, including regulating circadian rhythms, clearing free radicals, inhibiting biomolecular oxidation, suppressing neuroinflammation. Cumulative evidence indicates that melatonin wide range neuroprotective roles pathophysiological mechanisms signaling pathways. Moreover, levels decreased patients with diseases. In this review, we summarize current knowledge on regulation, molecular biological such as Alzheimer’s disease, Parkinson’s Huntington’s amyotrophic lateral sclerosis, vascular dementia multiple sclerosis. We also discuss clinical application disorders. This information will lead to better understanding regulation brain provide therapeutic options treatment

Language: Английский

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Exosomes induce endolysosomal permeabilization as a gateway by which exosomal tau seeds escape into the cytosol

Acta Neuropathologica, Journal Year: 2021, Volume and Issue: 141(2), P. 235 - 256

Published: Jan. 8, 2021

Abstract The microtubule-associated protein tau has a critical role in Alzheimer’s disease and other tauopathies. A proposed pathomechanism the progression of tauopathies is trans-synaptic spreading seeds, with for exosomes which are secretory nanovesicles generated by late endosomes. Our previous work demonstrated that brain-derived isolated from transgenic rTg4510 mice encapsulate seeds ability to induce aggregation recipient cells. We had also shown can hijack endosomal pathway spread through interconnected neurons. Here, we reveal how contained within internalized exploit mechanisms lysosomal degradation escape endosome cytosol HEK293T-derived ‘tau biosensor cells’. found majority exosome-containing endosomes fused lysosomes form endolysosomes. Exosomes induced their permeabilization, irrespective presence or whether exosomal preparations originated mouse brains HEK293T permeabilization conserved mechanism, operating both non-neuronal cells primary However, endolysosomes only occurred small fraction cells, supports notion occurs thresholded mechanism. Interestingly, was exhibited presenting this as an route into cytosol. Overexpression RAB7, required formation endolysosomes, strongly increased aggregation. Conversely, inhibition function alkalinizing agents, knocking-down decreased Together, conclude enzymatic activities permeabilize membranes, thereby facilitating access cytosolic its data underscore importance membrane integrity cellular invasion misfolded proteins resistant degradation.

Language: Английский

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