In vitro modulation of mTOR and mGlur5 influence α-synuclein accumulation. DOI Creative Commons

Viktoria Xing,

Kyle K. Biggar, Stephen S. G. Ferguson

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 23, 2023

Abstract One of the main hallmarks Parkinson’s disease (PD) is abnormal alpha-synuclein (α-syn) aggregation which forms component intracellular Lewy body inclusions. This short report used α-syn fibrils, as well an A53T mutant adenovirus to mimic conditions pathological protein in dopaminergic human derived SH-SY5Y neural cells. Since there evidence that mTOR pathway and glutamatergic signaling each influence aggregation, we also assessed impact inhibitor, rapamycin mGluR5 allosteric modulator, CTEP. We found both CTEP induced a significant reduction fibrils cells this effect was associated with factors (consistent enhanced autophagic activity). These data support possibility (or rapamycin) might be useful pharmacological approach target accumulation by promoting degradation or clearance.

Language: Английский

Apathy in Parkinson’s Disease: Clinical Patterns and Neurobiological Basis DOI Creative Commons
Matthieu Béreau, Vincent Van Waes, Mathieu Servant

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(12), P. 1599 - 1599

Published: June 10, 2023

Apathy is commonly defined as a loss of motivation leading to reduction in goal-directed behaviors. This multidimensional syndrome, which includes cognitive, emotional and behavioral components, one the most prevalent neuropsychiatric features Parkinson’s disease (PD). It has been established that prevalence apathy increases PD progresses. However, pathophysiology anatomic substrate this syndrome remain unclear. seems be underpinned by impaired anatomical structures link prefrontal cortex with limbic system. can encountered prodromal stage fluctuating patients receiving bilateral chronic subthalamic nucleus stimulation. In these stages, may considered disorder embodies amotivational combined dopaminergic serotonergic denervation dopa-responsive. contrast, advanced patients, cognitive announces decline dementia, diffuse neurotransmitter system dysfunction Lewy pathology spreading no longer review, we discuss clinical patterns their treatment, neurobiological basis apathy, potential role involved pathways motivational apathy.

Language: Английский

Citations

25

VGluT2 neuron subtypes in the paraventricular thalamic nucleus regulate depression in paraquat-induced Parkinson’s disease DOI
Yu Zhang,

Yihua Jiang,

Zhen Yu

et al.

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 472, P. 134559 - 134559

Published: May 9, 2024

Language: Английский

Citations

4

Eugenia uniflora Effects on the Depressive-like Behavior of MPTP-Exposed Female Rats: Apoptosis and α-Synuclein Modulation DOI Creative Commons
Anne Suély Pinto Savall,

Jhuly Dorneles de Mello,

Eduarda Monteiro Fidélis

et al.

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(1), P. 41 - 41

Published: Jan. 3, 2025

Background: Parkinson's disease (PD) is a neurodegenerative disorder marked by motor deficits and non-motor symptoms, such as depression, which are associated with dopaminergic loss α-synuclein aggregation in the brain. Objectives: This study investigated neuroprotective effects of hydroalcoholic extract purple fruit Eugenia uniflora (PFEU) on ability depressive-like behaviors PD model induced 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) female Wistar rats. Methods: Rats received intranasal administration MPTP or vehicle, followed 14 days oral PFEU (300 2000 mg/kg, administered once daily) vehicle. Depressive-like behavior was assessed using splash forced swimming tests, while evaluated rotarod open field tests. On day 15, hippocampal tissue collected for immunoreactivity analysis. Results: treatment behavior, significantly reversed PFEU, evidenced increased grooming decreased immobility. No coordination locomotion were observed. Furthermore, prevented MPTP-induced increase α-synuclein, p-p53, Bax restoring Bcl-2 levels, suggesting through modulation apoptotic pathways α-synuclein. Conclusions: These findings support PFEU's potential agent rats, highlighting its molecular mechanisms.

Language: Английский

Citations

0

Assessment of complementary white matter microstructural changes and grey matter atrophy in the 6-OHDA-induced model of Parkinson’s disease DOI
Maurizio Bergamino,

Alberto Fuentes,

Ivette M. Sandoval

et al.

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0

Prodromal Parkinson’s Disease DOI
Iro Boura, Karolina Popławska-Domaszewicz,

Naomi Limbachiya

et al.

Neurologic Clinics, Journal Year: 2025, Volume and Issue: 43(2), P. 209 - 228

Published: Jan. 22, 2025

Language: Английский

Citations

0

Attention-deficit/hyperactivity disorder-related psychomotor activity and altered neuronal activity in the medial prefrontal cortex and striatum in the A53T mouse model of Parkinson's disease and other synucleinopathies: Findings from an “endophenotype” approach DOI
Olga Dubljević, Željko Pavković, Maja Srbovan

et al.

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2025, Volume and Issue: unknown, P. 111273 - 111273

Published: Jan. 1, 2025

Language: Английский

Citations

0

Correlation of inflammatory markers with depression and sleep disorders accompanying the prodromal stage of Parkinson’s disease DOI
Chengguang Zhang, Yu Zhang, Ke Xu

et al.

World Journal of Psychiatry, Journal Year: 2025, Volume and Issue: 15(3)

Published: Feb. 26, 2025

Parkinson's disease (PD) is a common neurodegenerative disorder with increasing incidence and disability rates globally, placing heavy burden on patients their families. In the prodromal phase of PD, nonmotor symptoms, particularly depression sleep disorders, are frequent, profound effects progression patient quality life. Emerging research highlights critical role inflammatory markers-including interleukins tumor necrosis factor-in pathogenesis PD. These mediators participate in processes may induce or exacerbate depressive symptoms disorders by disrupting function hypothalamic-pituitary-adrenal axis affecting neurotransmitter, including serotonin, metabolism. Understanding correlations PD remains incomplete, limiting our ability to develop targeted interventions. This comprehensive review aims investigate specific between markers symptoms-particularly disorders-in The findings could have important practical applications, potentially leading development new diagnostic tools therapeutic strategies for managing By identifying understanding these correlations, healthcare providers better predict implement more effective treatments

Language: Английский

Citations

0

Multi-scale Neural Homeostasis Mechanisms: Insights into Neurodegenerative Diseases and Therapeutic Approaches, Including Exercise DOI Creative Commons
Ya Wang, Xuhui Chen, Cuntai Zhang

et al.

Advanced Exercise and Health Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0

Dysfunction of subthalamic dopaminergic circuitry contributes to anxiety- and depression-like behaviors in 6-OHDA lesion-induced hemiparkinsonian mice DOI
Jiaqi Zhang, Shuyi Li, Yin Cui

et al.

Acta Pharmacologica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: May 6, 2025

Language: Английский

Citations

0

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

2