A biological classification of Parkinson's disease: the SynNeurGe research diagnostic criteria

The Lancet Neurology, Journal Year: 2024, Volume and Issue: 23(2), P. 191 - 204

Published: Jan. 22, 2024

Language: Английский

---

Gastrointestinal and brain barriers: unlocking gates of communication across the microbiota–gut–brain axis

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2024, Volume and Issue: 21(4), P. 222 - 247

Published: Feb. 14, 2024

Crosstalk between gut and brain has long been appreciated in health disease, the microbiota is a key player communication these two distant organs. Yet, mechanisms through which influences development function of gut–brain axis remain largely unknown. Barriers present are specialized cellular interfaces that maintain strict homeostasis different compartments across this axis. These barriers include epithelial barrier, blood–brain barrier blood–cerebrospinal fluid barrier. ideally positioned to receive communicate microbial signals constituting gateway for gut–microbiota–brain communication. In Review, we focus on how modulation by can constitute an important channel Moreover, malfunction upon alterations composition could form basis various conditions, including often comorbid neurological gastrointestinal disorders. Thus, should unravelling molecular move from simplistic framing as 'leaky gut'. A mechanistic understanding barriers, especially during critical windows development, be aetiology The modulator This Review provides overview examines role disease.

Language: Английский

---

Gut liver brain axis in diseases: the implications for therapeutic interventions

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Dec. 6, 2023

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract, liver, and nervous systems. In past few decades, breakthrough progress has been made in gut liver brain axis, mainly through understanding its formation mechanism increasing treatment strategies. this review, we discuss various complex networks including barrier permeability, hormones, microbial metabolites, vagus nerve, neurotransmitters, immunity, toxic β-amyloid (Aβ) metabolism, epigenetic regulation gut-liver-brain axis. Some therapies containing antibiotics, probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), polyphenols, low FODMAP diet nanotechnology application regulate Besides, some special treatments targeting gut-liver include farnesoid X receptor (FXR) agonists, takeda G protein-coupled 5 (TGR5) glucagon-like peptide-1 (GLP-1) antagonists fibroblast growth factor 19 (FGF19) analogs. Targeting gut-brain embraces cognitive behavioral therapy (CBT), antidepressants tryptophan metabolism-related therapies. liver-brain contains Aβ future, better interactions will promote development novel preventative strategies discovery precise therapeutic targets multiple diseases.

Language: Английский

---

Emerging role of the host microbiome in neuropsychiatric disorders: overview and future directions

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(9), P. 3625 - 3637

Published: Sept. 1, 2023

Abstract The human body harbors a diverse ecosystem of microorganisms, including bacteria, viruses, and fungi, collectively known as the microbiota. Current research is increasingly focusing on potential association between microbiota various neuropsychiatric disorders. resides in parts body, such oral cavity, nasal passages, lungs, gut, skin, bladder, vagina. gut gastrointestinal tract has received particular attention due to its high abundance role psychiatric neurodegenerative However, presents other tissues, though less abundant, also plays crucial immune system homeostasis, thus influencing development progression For example, imbalance associated periodontitis might increase risk for Additionally, studies using postmortem brain samples have detected widespread presence bacteria brains patients with Alzheimer’s disease. This article provides an overview emerging host disorders discusses future directions, underlying biological mechanisms, reliable biomarkers microbiota, microbiota-targeted interventions, this field.

Language: Английский

---

Parkinson’s disease and gut microbiota: from clinical to mechanistic and therapeutic studies

Translational Neurodegeneration, Journal Year: 2023, Volume and Issue: 12(1)

Published: Dec. 15, 2023

Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases. The typical symptomatology PD includes motor symptoms; however, a range nonmotor symptoms, such as intestinal issues, usually occur before symptoms. Various microorganisms inhabiting gastrointestinal tract can profoundly influence physiopathology central nervous system through neurological, endocrine, and immune pathways involved in microbiota-gut-brain axis. In addition, extensive evidence suggests that gut microbiota strongly associated with PD. This review summarizes latest findings on microbial changes their clinical relevance, describes underlying mechanisms which bacteria may mediate PD, discusses correlations between microbes anti-PD drugs. this outlines status research therapies for future directions PD-gut research.

Language: Английский

---

Parkinson’s Disease is Predominantly a Genetic Disease

Journal of Parkinson s Disease, Journal Year: 2024, Volume and Issue: 14(3), P. 467 - 482

Published: March 26, 2024

The discovery of a pathogenic variant in the alpha-synuclein (SNCA) gene Contursi kindred 1997 indisputably confirmed genetic cause subset Parkinson’s disease (PD) patients. Currently, variants one seven established PD genes or strongest known risk factor gene, GBA1, are identified ∼15% patients unselected for age at onset and family history. In this Debate article, we highlight multiple avenues research that suggest an important - some cases even predominant role genetics aetiology, including familial clustering, high rates monogenic selected populations, complete penetrance with certain forms. At first sight, steep increase prevalence exceeding other neurodegenerative diseases may argue against etiology. Notably, principal contribution is conferred by LRRK2 GBA1 and, both cases, characterized overall late age-related penetrance. addition, polygenic plays considerable PD. However, it likely that, majority patients, complex interplay aging, genetic, environmental, epigenetic factors leads to development.

Language: Английский

---

Therapeutics for neurodegenerative diseases by targeting the gut microbiome: from bench to bedside

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Feb. 27, 2024

The aetiologies and origins of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's (PD), amyotrophic lateral sclerosis (ALS) Huntington's (HD), are complex multifaceted. A growing body evidence suggests that the gut microbiome plays crucial roles in development progression diseases. Clinicians have come to realize therapeutics targeting potential halt This narrative review examines alterations AD, PD, ALS HD, highlighting close relationship between brain Processes mediate microbiome-brain communication including immunological, vagus nerve circulatory pathways, evaluated. Furthermore, we summarize for diseases modify its metabolites, diets, probiotics prebiotics, microbial antibacterials faecal transplantation. Finally, current challenges future directions discussed.

Language: Английский

---

The immune system in Parkinson’s disease: what we know so far

Brain, Journal Year: 2024, Volume and Issue: unknown

Published: June 3, 2024

Abstract Parkinson's disease (PD) is characterised neuropathologically by the degeneration of dopaminergic neurons in ventral midbrain, accumulation α-synuclein (α-syn) aggregates neurons, and chronic neuroinflammation. In past two decades, vitro, ex vivo studies have consistently shown involvement inflammatory responses mediated microglia astrocytes, which may be elicited pathological α-syn or signals from affected other cell types, are directly linked to neurodegeneration development. Besides prominent immune alterations seen central nervous system (CNS), including infiltration T-cells into brain, more recent demonstrated important changes peripheral profile within both innate adaptive compartments, particularly involving monocytes, CD4+ CD8+ T-cells. This review aims integrate consolidated understanding immune-related processes underlying pathogenesis PD, focusing on cells, neuron-glia crosstalk as well central-peripheral interaction during development PD. Our analysis seeks provide a comprehensive view emerging knowledge mechanisms immunity PD implications this for better overall disease.

Language: Английский

---

BDNF/TrkB activators in Parkinson's disease: A new therapeutic strategy

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(10)

Published: May 1, 2024

Parkinson's disease (PD) is a neurodegenerative disorder of the brain and manifested by motor non-motor symptoms because degenerative changes in dopaminergic neurons substantia nigra. PD neuropathology associated with mitochondrial dysfunction, oxidative damage apoptosis. Thus, modulation apoptosis growth factors could be novel boulevard management PD. Brain-derived neurotrophic factor (BDNF) its receptor tropomyosin kinase type B (TrkB) are chiefly involved neuropathology. BDNF promotes survival nigra enhances functional activity striatal neurons. Deficiency TrkB triggers degeneration accumulation α-Syn As well, BDNF/TrkB signalling reduced early phase Targeting specific activators may attenuate this review aimed to discuss potential role against In conclusion, decreased linked severity long-term complications. Activation

Language: Английский

---

Fecal Microbiota Transplantation for Treatment of Parkinson Disease

JAMA Neurology, Journal Year: 2024, Volume and Issue: 81(9), P. 925 - 925

Published: July 29, 2024

Importance Dysbiosis has been robustly demonstrated in Parkinson disease (PD), and fecal microbiota transplantation (FMT) shown promising effects preclinical PD models. Objective To assess the safety symptomatic efficacy of colonic single-dose anaerobically prepared FMT. Design, Setting, Participants This was a double-blind, placebo-controlled, randomized clinical trial conducted between November 2020 June 2023 with follow-up period 12 months at 4 hospitals Finland. Patients aged 35 to 75 years Hoehn & Yahr stage 1-3 mild moderate symptom burden dysbiosis were included. Of 229 patients screened, 48 47 received intervention. One patient discontinued due worsening symptoms. Two further excluded before analysis 45 included intention-to-treat analysis. Intervention 2:1 ratio receive FMT or placebo via colonoscopy. Main Outcomes Measures The primary end point change Movement Disorder Society Unified Parkinson’s Disease Rating Scale parts I-III (part III off medication) 6 months. Safety assessed by recording adverse events (AEs). Results median (IQR) age 65 (52.5-70.0) group 66 (59.25-69.75) group; 9 (60.0%) 16 (53.3%) male group, respectively. outcome did not differ groups (0.97 points, 95% CI, −5.10 7.03, P = .75). Gastrointestinal AEs more frequent (16 [53%] vs 1 [7%]; .003). Secondary outcomes post hoc analyses showed stronger increase dopaminergic medication improvement certain motor nonmotor group. Microbiota changes pronounced after but differed donor. Nevertheless, status reversed frequently Conclusions Relevance safe offer clinically meaningful improvements. Further studies—for example, through modified approaches bowel cleansing—are warranted regarding specific impact donor composition conversion on as well needs PD. Trial Registration ClinicalTrials.gov Identifier: NCT04854291

Language: Английский

---