Ketogenic diet protects MPTP‐induced mouse model of Parkinson's disease via altering gut microbiota and metabolites DOI Creative Commons

Ziying Jiang,

Xinyu Wang, Haoqiang Zhang

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 16, 2023

Abstract The ketogenic diet (KD) is a low‐carbohydrate, high‐fat regime that protective against neurodegenerative diseases. However, the impact of KD on Parkinson's disease (PD) and its mechanisms remains unclear. 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced mouse model PD was fed with for 8 weeks. Motor function dopaminergic neurons were evaluated. Inflammation in brain, plasma, colon tissue also measured. Fecal samples assessed by 16S rDNA gene sequencing untargeted metabolomics. We found protected motor dysfunction, neuron loss, inflammation an MPTP PD. revealed administration significantly increased Citrobacter , Desulfovibrio Ruminococcus decreased Dubosiella whereas treatment reversed dysbiosis. Meanwhile, regulated MPTP‐induced histamine, N‐acetylputrescine, d ‐aspartic acid, other metabolites. microbiota transplantation using feces from KD‐treated mice attenuated impairment loss antibiotic‐pretreated mice. Our current study demonstrates played neuroprotective role through diet–gut microbiota–brain axis, which may involve brain colon. future research warranted to explore explicit anti‐inflammatory gut–brain axis models KD.

Language: Английский

Evolving Landscape of Parkinson’s Disease Research: Challenges and Perspectives DOI Creative Commons
Rumiana Koynova, Janet M. Sasso, Qiongqiong Angela Zhou

et al.

ACS Omega, Journal Year: 2025, Volume and Issue: 10(2), P. 1864 - 1892

Published: Jan. 8, 2025

Parkinson's disease (PD) is a progressive neurodegenerative disorder that primarily affects movement. It occurs due to gradual deficit of dopamine-producing brain cells, particularly in the substantia nigra. The precise etiology PD not fully understood, but it likely involves combination genetic and environmental factors. therapies available at present alleviate symptoms do stop disease's advancement. Research endeavors are currently directed inventing disease-controlling aim inherent mechanisms PD. biomarker breakthroughs hold enormous potential: earlier diagnosis, better monitoring, targeted treatment based on individual response could significantly improve patient outcomes ease burden this disease. research an active evolving field, focusing understanding mechanisms, identifying biomarkers, developing new treatments, improving care. In report, we explore data from CAS Content Collection outline progress We analyze publication landscape offer perspective into latest expertise advancements. Key emerging concepts reviewed strategies fight evaluated. Pharmacological targets, risk factors, as well comorbid diseases explored, clinical usage products against with their production pipelines trials for drug repurposing examined. This review aims comprehensive overview advancing current about PD, define challenges, assess growth prospects stimulate efforts battling

Language: Английский

Citations

3
Functional brain networks in the evaluation of patients with neurodegenerative disorders DOI
Matej Perovnik, Tomaž Rus, Katharina A. Schindlbeck

et al.

Nature Reviews Neurology, Journal Year: 2022, Volume and Issue: 19(2), P. 73 - 90

Published: Dec. 20, 2022

Language: Английский

Citations

52
Mitophagy and reactive oxygen species interplay in Parkinson’s disease DOI Creative Commons
Bin Xiao,

Joshua Kuruvilla,

Eng‐King Tan

et al.

npj Parkinson s Disease, Journal Year: 2022, Volume and Issue: 8(1)

Published: Oct. 18, 2022

Mitophagy impairment and oxidative stress are cardinal pathological hallmarks in Parkinson's disease (PD), a common age-related neurodegenerative condition. The specific interactions between mitophagy reactive oxygen species (ROS) have attracted considerable attention even though their exact interplay PD has not been fully elucidated. We highlight the ROS mitophagy, with focus on signalling pathways downstream to that triggers draw potential therapeutic compounds target these both experimental clinical models. Identifying combination of inhibitors activators provide physiologic balance this complex may lead more optimal outcome. Deciphering temporal relationship early course neurodegeneration can unravel mechanistic clues potentially development for drug trials focusing prodromic or at-risk individuals.

Language: Английский

Citations

51
Advances in quantum dot-based biosensors for DNA-modifying enzymes assay DOI
Qian Zhang, Xinyi Zhang, Fei Ma

et al.

Coordination Chemistry Reviews, Journal Year: 2022, Volume and Issue: 469, P. 214674 - 214674

Published: June 22, 2022

Language: Английский

Citations

47
GSK-3β: An exuberating neuroinflammatory mediator in Parkinson's disease DOI Creative Commons
Sabiya Samim Khan,

Sushmita Janrao,

Saurabh Srivastava

et al.

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 210, P. 115496 - 115496

Published: March 11, 2023

Neuroinflammation is a critical degradative condition affecting neurons in the brain. Progressive neurodegenerative conditions such as Alzheimer's disease and Parkinson's (PD) have been strongly linked to neuroinflammation. The trigger point for inflammatory cells body physiological immune system. response mediated by glial astrocytes can rectify alterations occurring cell time being but prolonged activation leads pathological progression. proteins mediating an response, per available literature, are undoubtedly GSK-3β, NLRP3, TNF, PPARγ, NF-κB, along with few other mediatory proteins. NLRP3 inflammasome undeniably principal instigator of neuroinflammatory regulatory pathways controlling its still unclear, besides less clarity interplay between different Recent reports suggested involvement GSK-3β regulating activation, exact mechanistic pathway remains vague. In current review, we attempt provide elaborate description crosstalk markers neuroinflammation progression, linking it transcription factors posttranslational modification recent clinical therapeutic advances targeting these also discussed parallel comprehensive view progress made PD management lacunas existing field.

Language: Английский

Citations

40
Pros and cons for statins use and risk of Parkinson's disease: An updated perspective DOI Creative Commons
Hayder M. Al‐kuraishy, Ali I. Al‐Gareeb, Αθανάσιος Αλεξίου

et al.

Pharmacology Research & Perspectives, Journal Year: 2023, Volume and Issue: 11(2)

Published: Feb. 22, 2023

Parkinson's disease (PD) is the second most frequent neurodegenerative brain (NBD) after Alzheimer's (AD). Statins are common lipid-lowering agents used in management of dyslipidemia and prevention primary secondary cardiovascular diseases (CVD) events. In addition, there a controversial point regarding role serum lipids pathogenesis PD. this bargain, as statins reduce cholesterol so they affect PD neuropathology bidirectional ways either protective or harmful. not PD, but frequently disorders commonly associated with elderly population. Therefore, use that population may outcomes. Concerning potential on neuropathology, conflicts controversies against development harmful by increasing risk for review aimed to clarify precise pros cons from published studies. Many studies suggest through modulation inflammatory lysosomal signaling pathways. Nevertheless, other observations statin therapy increase diverse mechanisms including reduction CoQ10. conclusion, strong neuropathology. retrospective prospective necessary regard.

Language: Английский

Citations

39
Current Treatments and New, Tentative Therapies for Parkinson’s Disease DOI Creative Commons
Teresa Pardo-Moreno, Victoria García‐Morales, Nora Suleiman‐Martos

et al.

Pharmaceutics, Journal Year: 2023, Volume and Issue: 15(3), P. 770 - 770

Published: Feb. 25, 2023

Parkinson’s disease (PD) is a neurodegenerative pathology, the origin of which associated with death neuronal cells involved in production dopamine. The prevalence PD has increased exponentially. aim this review was to describe novel treatments for that are currently under investigation and study possible therapeutic targets. pathophysiology based on formation alpha-synuclein folds generate Lewy bodies, cytotoxic reduce dopamine levels. Most pharmacological target symptoms. These include aimed at reducing accumulation (epigallocatechin), its clearance via immunotherapy, inhibiting LRRK2, upregulating cerebrosidase (ambroxol). continues be pathology unknown generates significant social cost patients who suffer from it. Although there still no definitive cure present, numerous available symptomatology addition other alternatives investigation. However, approach should combination non-pharmacological strategies maximise outcomes improve symptomatological control these patients. It therefore necessary delve deeper into order quality life

Language: Английский

Citations

39
Lewy bodies, iron, inflammation and neuromelanin: pathological aspects underlying Parkinson’s disease DOI Creative Commons
Peter Riederer, Toshiharu Nagatsu, Moussa B. H. Youdim

et al.

Journal of Neural Transmission, Journal Year: 2023, Volume and Issue: 130(5), P. 627 - 646

Published: April 16, 2023

Abstract Since the description of some peculiar symptoms by James Parkinson in 1817, attempts have been made to define its cause or at least enlighten pathology “Parkinson’s disease (PD).” The vast majority PD subtypes and most cases sporadic share Lewy bodies (LBs) as a characteristic pathological hallmark. However, processes underlying LBs generation causal triggers are still unknown. ɑ-Synuclein (ɑ-syn, encoded SNCA gene) is major component LBs, missense mutations duplications/triplications for rare hereditary forms PD. Thus, it imperative study ɑ-syn protein pathology, including oligomerization, fibril formation, aggregation, spreading mechanisms. Furthermore, there synergistic effects pathogenic mechanisms PD, multiple factors—contributing with different ratios—appear be progression factors. For example, oxidative stress, reduced antioxidative capacity, mitochondrial dysfunction, proteasomal disturbances each suggested formation aggregation contribute neuroinflammation neural cell death. Aging also risk factor Iron, well neuromelanin (NM), show age-dependent increases, iron significantly increased Parkinsonian substantia nigra (SN). Iron-induced include changes molecular structure ɑ-syn. more recent research demonstrates that (i) detected not only dopaminergic neurons glia but various neurotransmitter systems, (ii) sympathetic nerve fibres degenerate first, (iii) “brain-first” deficiency evident before induced NM. These findings support ɑ-syn/LBs iron- NM-induced important facts via their interaction potentiate process SN. As such, multifactorial toxic posted on personal genetic assumed neurodegenerative Differences ratios factors spatiotemporal development, fact common hard identify, imply existence several phenotypical subtypes, which supported arguments from both “bottom-up/dual-hit” models. Therapeutic strategies necessary avoid single initiation leading

Language: Английский

Citations

35
NF‐κB/NLRP3 inflammasome axis and risk of Parkinson's disease in Type 2 diabetes mellitus: A narrative review and new perspective DOI Creative Commons
Mohammed Alrouji, Hayder M. Al‐kuraishy, Ali I. Al‐Gareeb

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2023, Volume and Issue: 27(13), P. 1775 - 1789

Published: May 21, 2023

Abstract Parkinson's disease (PD) is the second most common neurodegenerative after Alzheimer's (AD). Genetic predisposition and immune dysfunction are involved in pathogenesis of PD. Notably, peripheral inflammatory disorders neuroinflammation associated with PD neuropathology. Type 2 diabetes mellitus (T2DM) due to hyperglycaemia‐induced oxidative stress release pro‐inflammatory cytokines. Particularly, insulin resistance (IR) T2DM promotes degeneration dopaminergic neurons substantia nigra (SN). Thus, T2DM‐induced predispose development progression PD, their targeting may reduce risk T2DM. Therefore, this narrative review aims find potential link between by investigating role signalling pathways, mainly nuclear factor kappa B (NF‐κB) nod‐like receptor pyrin 3 (NLRP3) inflammasome. NF‐κB implicated T2DM, activation induction neuronal apoptosis was also confirmed patients. Systemic NLRP3 inflammasome accumulation α‐synuclein SN. Increasing patients enhances interleukin (IL)‐1β followed systemic inflammation neuroinflammation. In conclusion, NF‐κB/NLRP3 axis could be causal pathway The mechanisms triggered activated lead pancreatic β‐cell attenuation changes inhibiting early future risk.

Language: Английский

Citations

33
The Endotoxin Hypothesis of Parkinson's Disease DOI Creative Commons
Guy C. Brown,

Marta Camacho,

Caroline H. Williams‐Gray

et al.

Movement Disorders, Journal Year: 2023, Volume and Issue: 38(7), P. 1143 - 1155

Published: May 8, 2023

The endotoxin hypothesis of Parkinson's disease (PD) is the idea that lipopolysaccharide (LPS) endotoxins contribute to pathogenesis this disorder. LPS are found in, and released from, outer membrane Gram-negative bacteria, for example in gut. It proposed gut dysfunction early PD leads elevated levels wall blood, which promotes both α-synuclein aggregation enteric neurons a peripheral inflammatory response. Communication brain via circulating cytokines blood and/or gut-brain axis neuroinflammation spreading pathology, exacerbating neurodegeneration brainstem nuclei loss dopaminergic substantia nigra, manifesting clinical symptoms PD. evidence supporting includes: (1) dysfunction, permeability, bacterial changes occur PD, (2) serum increased proportion patients, (3) induces expression, aggregation, neurotoxicity, (4) causes activation monocytes leading cytokine production, (5) inflammation specific midbrain neurons, mediated by microglia. If correct, then treatment options might include: changing microbiome, reducing levels, or blocking response immune cells microglia LPS. However, has number limitations requires further testing, particular whether can reduce incidence, progression, severity. © 2023 Authors. Movement Disorders published Wiley Periodicals LLC on behalf International Parkinson Disorder Society.

Language: Английский

Citations

30