Methamphetamine Increases Tubulo-Vesicular Areas While Dissipating Proteins from Vesicles Involved in Cell Clearance DOI Open Access
Gloria Lazzeri, Paola Lenzi, Carla L. Busceti

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9601 - 9601

Published: Sept. 4, 2024

Cytopathology induced by methamphetamine (METH) is reminiscent of degenerative disorders such as Parkinson’s disease, and it characterized membrane organelles arranged in tubulo-vesicular structures. These areas, appearing clusters vesicles, have never been defined concerning the presence specific organelles. Therefore, present study aimed to identify relative absolute area membrane-bound following a moderate dose (100 µM) METH administered catecholamine-containing PC12 cells. Organelles antigens were detected immunofluorescence, they further quantified plain electron microscopy situ stoichiometry. This analysis indicated an increase autophagosomes damaged mitochondria along with decrease lysosomes healthy mitochondria. Following METH, severe dissipation hallmark proteins from their own vesicles was measured. In fact, amounts LC3 p62 reduced within autophagy vacuoles compared whole cytosol. Similarly, LAMP1 Cathepsin-D reduced. findings suggest loss compartmentalization confirm competence cell clearing during catecholamine degeneration. Such entropy consistent energy stores, which routinely govern appropriate subcellular compartmentalization.

Language: Английский

Targeting mitophagy in neurodegenerative diseases DOI
Odetta Antico, Paul Thompson, Nicholas T. Hertz

et al.

Nature Reviews Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Language: Английский

Citations

6
Alpha-Synuclein Effects on Mitochondrial Quality Control in Parkinson’s Disease DOI Creative Commons
Liyan Shen, Ulf Dettmer

Biomolecules, Journal Year: 2024, Volume and Issue: 14(12), P. 1649 - 1649

Published: Dec. 22, 2024

The maintenance of healthy mitochondria is essential for neuronal survival and relies upon mitochondrial quality control pathways involved in biogenesis, dynamics, autophagy (mitophagy). Mitochondrial dysfunction critically implicated Parkinson’s disease (PD), a brain disorder characterized by the progressive loss dopaminergic neurons substantia nigra. Consequently, impaired may play key role PD pathology. This affirmed work indicating that genes such as PRKN PINK1, which participate multiple processes, harbor PD-associated mutations. Furthermore, complex-I-inhibiting toxins like MPTP rotenone are known to cause Parkinson-like symptoms. At heart alpha-synuclein (αS), small synaptic protein misfolds aggregates form disease’s hallmark Lewy bodies. specific mechanisms through aggregated αS exerts its neurotoxicity still unknown; however, given vital both PD, an understanding how influences be elucidating pathogenesis discovering future therapeutic targets. Here, current knowledge relationship between reviewed, highlighting recent findings regarding effects on autophagy.

Language: Английский

Citations

4
Alpha-synuclein expression in anterior pituitary cells of aged cattle DOI
Yvan Bienvenu Niyonzima,

Denis Karani Wanjiru,

Yuuki Asato

et al.

Domestic Animal Endocrinology, Journal Year: 2025, Volume and Issue: 92, P. 106936 - 106936

Published: March 1, 2025

Language: Английский

Citations

0
Mitochondria-targeted oligomeric α-synuclein induces TOM40 degradation and mitochondrial dysfunction in Parkinson’s disease and parkinsonism-dementia of Guam DOI Creative Commons
Velmarini Vasquez, Manohar Kodavati, Joy Mitra

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(12)

Published: Dec. 18, 2024

Abstract Mitochondrial dysfunction is a central aspect of Parkinson’s disease (PD) pathology, yet the underlying mechanisms are not fully understood. This study investigates link between α-Synuclein (α-Syn) pathology and loss translocase outer mitochondrial membrane 40 (TOM40), unraveling its implications for dysfunctions in neurons. We discovered that TOM40 protein depletion occurs brains patients with Guam Parkinsonism-Dementia (Guam PD) cultured neurons expressing α-Syn proteinopathy, notably, without corresponding changes mRNA levels. Cultured mutants, or mitochondria-targeting signal (MTS) underscores role α-Syn’s localization inducing degradation. PDe-related etiological factors, such as 6-hydroxydopamine ROS/metal ions stress, which promotes oligomerization, exacerbate PD patient-derived cells SNCA gene triplication. Although interacts both TOM20 membrane, degradation selective TOM40, via ubiquitin-proteasome system (UPS) pathway. Our comprehensive analyses using Seahorse technology, DNA sequencing, damage assessments, demonstrate mutant α-Syn-induced results dysfunction, characterized by reduced potential, accumulation mtDNA damage, deletion/insertion mutations, altered oxygen consumption rates. Notably, ectopic supplementation reducing pathological forms ADP-ribosylation inhibitors ameliorate these defects, suggesting potential therapeutic avenues. In conclusion, our findings provide crucial mechanistic insights into how leads to offering targeted interventions alleviate defects PD.

Language: Английский

Citations

2
Alpha Synuclein Toxicity and Non-Motor Parkinson’s DOI Creative Commons
G. Mazzotta, Carmela Conte

Cells, Journal Year: 2024, Volume and Issue: 13(15), P. 1265 - 1265

Published: July 27, 2024

Parkinson's disease (PD) is a common multisystem neurodegenerative disorder affecting 1% of the population over age 60 years. The main neuropathological features PD are loss dopaminergic neurons in substantia nigra pars compacta (SNpc) and presence alpha synuclein (αSyn)-rich Lewy bodies both manifesting with classical motor signs. αSyn has emerged as key protein pathology it can spread through synaptic networks to reach several anatomical regions body contributing appearance non-motor symptoms (NMS) considered prevalent among individuals prior diagnosis persisting throughout patient's life. NMS mainly includes taste smell, constipation, psychiatric disorders, dementia, impaired rapid eye movement (REM) sleep, urogenital dysfunction, cardiovascular impairment. This review summarizes more recent findings on impact deposits prodromal emphasizes importance early detection toxic species biofluids peripheral biopsies prospective biomarkers PD.

Language: Английский

Citations

1
Alpha Synuclein Toxicity and Non-motor Parkinson’s DOI Open Access
G. Mazzotta, Carmela Conte

Published: June 18, 2024

Parkinson’s disease (PD) is a common multisystem neurodegenerative disorder affecting 1% of the population above 60 years. The main neuropathological features PD are loss dopaminergic neurons in substantia nigra pars compacta (SNpc) and presence alpha synuclein (Syn)-rich Lewy bodies both manifesting with classical motor signs. Syn has emerged as key protein pathology it can spread through synaptic networks to reach several anatomical regions body contributing appearance non-motor symptoms (NMS) considerate prevalent among individuals before diagnosis persisting throughout patient’s life. NMS mainly include taste smell, constipation, psychiatric disorders, dementia, rapid eye movement (REM) sleep behavior impairment, urogenital dysfunction, cardiovascular impairment. This review summarizes more recent findings showing impact deposits on prodromal emphasizes importance early detection toxic species biofluids peripheral biopsies prospective biomarkers PD.

Language: Английский

Citations

0
High frequency electrical stimulation reduces α-synuclein levels and α-synuclein-mediated autophagy dysfunction DOI Creative Commons
Jimmy George,

Kashfia Shafiq,

Minesh Kapadia

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 12, 2024

Abstract Accumulation of α-synuclein (α-Syn) has been implicated in proteasome and autophagy dysfunction Parkinson’s disease (PD). High frequency electrical stimulation (HFS) mimicking clinical parameters used for deep brain (DBS) vitro or DBS vivo preclinical models PD have found to reduce levels α-Syn and, certain cases, provide possible neuroprotection. However, the mechanisms by which this reduction improves cellular associated with accumulation remains elusive. Using HFS that recapitulate vitro, we led a mutant thereby limited impairments due α-Syn. Additionally, observed modulates via ATP6V0C subunit V-ATPase mitigates mediated autophagic dysfunction. This study highlights role may prove be viable approach decrease pathological protein neurodegeneration.

Language: Английский

Citations

0
Methamphetamine Increases Tubulo-Vesicular Areas While Dissipating Proteins from Vesicles Involved in Cell Clearance DOI Open Access
Gloria Lazzeri, Paola Lenzi, Carla L. Busceti

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9601 - 9601

Published: Sept. 4, 2024

Cytopathology induced by methamphetamine (METH) is reminiscent of degenerative disorders such as Parkinson’s disease, and it characterized membrane organelles arranged in tubulo-vesicular structures. These areas, appearing clusters vesicles, have never been defined concerning the presence specific organelles. Therefore, present study aimed to identify relative absolute area membrane-bound following a moderate dose (100 µM) METH administered catecholamine-containing PC12 cells. Organelles antigens were detected immunofluorescence, they further quantified plain electron microscopy situ stoichiometry. This analysis indicated an increase autophagosomes damaged mitochondria along with decrease lysosomes healthy mitochondria. Following METH, severe dissipation hallmark proteins from their own vesicles was measured. In fact, amounts LC3 p62 reduced within autophagy vacuoles compared whole cytosol. Similarly, LAMP1 Cathepsin-D reduced. findings suggest loss compartmentalization confirm competence cell clearing during catecholamine degeneration. Such entropy consistent energy stores, which routinely govern appropriate subcellular compartmentalization.

Language: Английский

Citations

0