Coupled Spatio-Temporal Dynamics and Nonlocality in Advanced Mathematical Models for the Analysis of Complex Neurodegenerative Disease Pathologies DOI Creative Commons
Swadesh Pal, Roderick Melnik

Published: Jan. 1, 2023

One in six of the world’s population has to deal with neurodegenerative disorders, and while medical devices exist detect, prevent, treat such some fundamentals progression associated diseases remain ambiguous. In this contribution, we focus on Alzheimer’s disease (AD), where amyloid-beta (Aβ) tau proteins are among main contributors development or propagation AD. The Aβ clump together form plaques disrupt cell functions. Moreover, abnormal chemical change brain helps build sticky tangles that block neuron’s transport system. Astrocytes generally maintain a healthy balance by clearing toxic plaques. Even so, over-activated astrocytes release chemokines cytokines also react pro-inflammatory cytokines, further increasing production Aβ. We have provided details novel coupled mathematical model can capture astrocytes’ dual behaviour, emphasizing importance spatio-temporal coupling nonlocality. demonstrated depends memory effects, is disease’s earlier status, which involves non-Markovian processes. explained how integrate connectome data network study effect, as well role phenomenon. Depending loads brain, discussed analysis neuronal damage brain. effect slow down decreasing rate damage. Representative numerical examples been given, special attention paid nonequilibrium considerations stochastic modelling frameworks diseases.

Language: Английский

Calcium-mediated regulation of mitophagy: implications in neurodegenerative diseases DOI Creative Commons
Fivos Borbolis, Christina Ploumi, Konstantinos Palikaras

et al.

npj Metabolic Health and Disease, Journal Year: 2025, Volume and Issue: 3(1)

Published: Feb. 3, 2025

Language: Английский

Citations

1
Investigating the Interplay between Mitophagy and Diabetic Neuropathy: Uncovering the hidden secrets of the disease pathology DOI Creative Commons
Kiavash Hushmandi, Behzad Einollahi,

Rachel Aow

et al.

Pharmacological Research, Journal Year: 2024, Volume and Issue: 208, P. 107394 - 107394

Published: Sept. 3, 2024

Mitophagy, the cellular process of selectively eliminating damaged mitochondria, plays a crucial role in maintaining metabolic balance and preventing insulin resistance, both key factors type 2 diabetes mellitus (T2DM) development. When mitophagy malfunctions diabetic neuropathy, it triggers cascade disruptions, including reduced energy production, increased oxidative stress, cell death, ultimately leading to various complications. Thus, targeting enhance may have emerged as promising therapeutic strategy for T2DM its Notably, plant-derived compounds with β-cell protective mitophagy-stimulating properties offer potential novel agents. This review highlights intricate mechanisms linking dysfunction complications, particularly elucidating interventions this debilitating disease.

Language: Английский

Citations

5
Age‐specific and compartment‐dependent changes in mitochondrial homeostasis and cytoplasmic viscosity in mouse peripheral neurons DOI Creative Commons
James N. Sleigh, Francesca Mattedi, Sandy Richter

et al.

Aging Cell, Journal Year: 2024, Volume and Issue: unknown

Published: June 17, 2024

Abstract Mitochondria are dynamic bioenergetic hubs that become compromised with age. In neurons, declining mitochondrial axonal transport has been associated reduced cellular health. However, it is still unclear to what extent the decline of and function observed during ageing coupled, if somal mitochondria display compartment‐specific features make them more susceptible process. It also not known whether biophysical state cytoplasm, thought affect many functions, changes age impact trafficking homeostasis. Focusing on mouse peripheral nervous system, we show age‐dependent in accompanied by reduction membrane potential intramitochondrial viscosity, but calcium buffering, both mitochondria. Intriguingly, observe a specific increase cytoplasmic viscosity neuronal cell body, where most polarised, which correlates decreased diffusiveness. Increasing crowding somatic compartment DRG neurons grown microfluidic chambers reduces trafficking, suggesting mechanistic link between regulation dynamics. Our work provides reference for studying relationship homeostasis viscoelasticity cytoplasm compartment‐dependent manner ageing.

Language: Английский

Citations

3
The life and times of brain autophagic vesicles DOI
Lisa Gambarotto, Erin Wosnitzka, Vassiliki Nikoletopoulou

et al.

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169105 - 169105

Published: March 1, 2025

Language: Английский

Citations

0
GPR50 regulates neuronal development as a mitophagy receptor DOI Creative Commons

Ji-Chuan Liu,

Xiu‐Yun Zhao,

Ming-Lei Wu

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(8)

Published: Aug. 15, 2024

Abstract Neurons rely heavily on high mitochondrial metabolism to provide sufficient energy for proper development. However, it remains unclear how neurons maintain oxidative phosphorylation (OXPHOS) during Mitophagy plays a pivotal role in maintaining quality and quantity. We herein describe that G protein-coupled receptor 50 (GPR50) is novel mitophagy receptor, which harbors the LC3-interacting region (LIR) required under stress conditions. Although does not localize mitochondria normal culturing conditions, GPR50 recruited depolarized membrane upon stress, marks portion recruits assembling autophagosomes, eventually facilitating fragments be engulfed by autophagosomes. Mutations Δ502-505 T532A attenuate GPR50-mediated disrupting binding of LC3 recruitment GPR50. Deficiency causes accumulation damaged disrupts OXPHOS, resulting insufficient ATP production excessive ROS generation, impairing neuronal GPR50-deficient mice exhibit impaired social recognition, rescued prenatal treatment with mitoQ, mitochondrially antioxidant. The present study identifies as OXPHOS developing neurons.

Language: Английский

Citations

1
Mitostasis in age-associated neurodegeneration DOI
Mrutyunjaya Panda, Maria Markaki, Nektarios Tavernarakis

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: unknown, P. 167547 - 167547

Published: Oct. 1, 2024

Language: Английский

Citations

1
Optic Nerve Astrocytes DOI
Song Li

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Language: Английский

Citations

0
Coupled Spatio-Temporal Dynamics and Nonlocality in Advanced Mathematical Models for the Analysis of Complex Neurodegenerative Disease Pathologies DOI Creative Commons
Swadesh Pal, Roderick Melnik

Published: Jan. 1, 2023

One in six of the world’s population has to deal with neurodegenerative disorders, and while medical devices exist detect, prevent, treat such some fundamentals progression associated diseases remain ambiguous. In this contribution, we focus on Alzheimer’s disease (AD), where amyloid-beta (Aβ) tau proteins are among main contributors development or propagation AD. The Aβ clump together form plaques disrupt cell functions. Moreover, abnormal chemical change brain helps build sticky tangles that block neuron’s transport system. Astrocytes generally maintain a healthy balance by clearing toxic plaques. Even so, over-activated astrocytes release chemokines cytokines also react pro-inflammatory cytokines, further increasing production Aβ. We have provided details novel coupled mathematical model can capture astrocytes’ dual behaviour, emphasizing importance spatio-temporal coupling nonlocality. demonstrated depends memory effects, is disease’s earlier status, which involves non-Markovian processes. explained how integrate connectome data network study effect, as well role phenomenon. Depending loads brain, discussed analysis neuronal damage brain. effect slow down decreasing rate damage. Representative numerical examples been given, special attention paid nonequilibrium considerations stochastic modelling frameworks diseases.

Language: Английский

Citations

0