Chronic DSS-Induced Colitis Exacerbates Parkinson’s Disease
Phenotype and Its Pathological Features Following Intragastric
Rotenone Exposure

J 2025

Chronic DSS-Induced Colitis Exacerbates Parkinson’s Disease Phenotype and Its Pathological Features Following Intragastric Rotenone Exposure

SHARMA, Nishant; Monica SHARMA; Disha THAKKAR; Hemant KUMAR; Soňa SMETANOVÁ et. al.

Základní údaje

Originální název

Chronic DSS-Induced Colitis Exacerbates Parkinson’s Disease Phenotype and Its Pathological Features Following Intragastric Rotenone Exposure

Název česky

Chronická kolitida vyvolaná DSS zhoršuje fenotyp Parkinsonovy nemoci a její patologické rysy po expozici rotenonu v žaludku

Autoři

SHARMA, Nishant; Monica SHARMA; Disha THAKKAR; Hemant KUMAR; Soňa SMETANOVÁ; Lucie BUREŠOVÁ; Petr ANDRLA a Amit Suresh KHAIRNAR

Vydání

ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE, WASHINGTON, AMER CHEMICAL SOC, 2025, 2575-9108

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Česká republika

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.700 v roce 2024

Organizační jednotka

Lékařská fakulta

DOI

https://doi.org/10.1021/acsptsci.4c00286

UT WoS

001406692300001

EID Scopus

2-s2.0-85217053427

Klíčová slova anglicky

Parkinson’s disease; gut inflammation; inflammatory bowel disease; α synuclein; gut–brain axis

Štítky

14110132, 14110515, 143180, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 27. 5. 2025 14:11, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

Parkinson’s disease (PD) is not just reflective of synucleinopathies that affect the brain but also the gastrointestinal (GI) tract. (1) The pathological features of PD include the loss of dopaminergic (DAergic) neurons within substantia nigra pars compacta (SNpc), as well as the appearance of intraneuronal inclusions known as Lewy bodies or Lewy neurites, which are primarily composed of self-aggregatory protein α-synuclein (α-syn). (2) Globally, an estimated 6.2 million people are believed to have PD and its prevalence is expected to increase 2.5-fold by 2040. (3) In addition, recent epidemiological research also suggests that PD patients have a variety of prodromal GI dysfunctions, including delayed gastric emptying, infrequent bowel movements, and chronic constipation, decades before they acquire centrally driven motor deficits of PD. (4) Correspondingly, GI tissue of PD patients has shown changes in functional and structural activities during the early stage of the disease, including the presence of α-syn-containing inclusions, impaired mucosal barrier function, and altered bacterial composition. (5,6) The presentation of GI pathology is linked with the Braak hypothesis, which states that ingestion/inhalation of unknown environmental triggers causes the development of α-syn pathology first in the enteric nervous system (ENS), followed by impacted lower brain stem regions, such as the dorsal motor nucleus of the vagus nerve (DMV), locus coeruleus (LC), and subsequently to the SNpc, where it induces death of DAergic neurons. (7) In support of this, several preclinical studies have recently demonstrated transneuronal transfer of injected recombinant α-syn into the gut wall to the brain via the vagal nerve. (8−10) Clinical studies have also revealed that complete truncal vagotomy is now linked to a lower risk of PD. (11) These reports indicate that enteric α-syn pathology can spread from the GI tract to the brain. Still, only a few studies have been conducted to explain the molecular mechanism associated with the development of enteric α-syn pathology and its long-distance upward transmission to the brain.

Návaznosti

LM2023069, projekt VaV

Název: Výzkumná infrastruktura RECETOX

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Výzkumná infrastruktura RECETOX

LX22NPO5107, projekt VaV

Název: Národní ústav pro neurologický výzkum

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní ústav pro neurologický výzkum, 5.1 EXCELES

857560, interní kód MU
(Kód CEP: EF17_043/0009632)

Název: CETOCOEN Excellence (Akronym: CETOCOEN Excellence)

Investor: Evropská unie, CETOCOEN Excellence, Spreading excellence and widening participation

Citovat

SHARMA, Nishant; Monica SHARMA; Disha THAKKAR; Hemant KUMAR; Soňa SMETANOVÁ; Lucie BUREŠOVÁ; Petr ANDRLA a Amit Suresh KHAIRNAR. Chronic DSS-Induced Colitis Exacerbates Parkinson’s Disease Phenotype and Its Pathological Features Following Intragastric Rotenone Exposure. ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE. WASHINGTON: AMER CHEMICAL SOC, 2025, roč. 8, č. 2, s. 346-367. ISSN 2575-9108. Dostupné z: https://doi.org/10.1021/acsptsci.4c00286.

@article{2478501,
   author = {Sharma, Nishant and Sharma, Monica and Thakkar, Disha and Kumar, Hemant and Smetanová, Soňa and Burešová, Lucie and Andrla, Petr and Khairnar, Amit Suresh},
   article_location = {WASHINGTON},
   article_number = {2},
   doi = {https://doi.org/10.1021/acsptsci.4c00286},
   keywords = {Parkinson’s disease; gut inflammation; inflammatory bowel disease; α synuclein; gut–brain axis},
   language = {eng},
   issn = {2575-9108},
   journal = {ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE},
   note = {Nedoplňovat EF17_043/0009632.},
   title = {Chronic DSS-Induced Colitis Exacerbates Parkinson’s Disease Phenotype and Its Pathological Features Following Intragastric Rotenone Exposure},
   url = {https://pubs.acs.org/doi/full/10.1021/acsptsci.4c00286},
   volume = {8},
   year = {2025}
}

TY  - JOUR
ID  - 2478501
AU  - Sharma, Nishant - Sharma, Monica - Thakkar, Disha - Kumar, Hemant - Smetanová, Soňa - Burešová, Lucie - Andrla, Petr - Khairnar, Amit Suresh
PY  - 2025
TI  - Chronic DSS-Induced Colitis Exacerbates Parkinson’s Disease Phenotype and Its Pathological Features Following Intragastric Rotenone Exposure
JF  - ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
VL  - 8
IS  - 2
SP  - 346-367
EP  - 346-367
PB  - AMER CHEMICAL SOC
SN  - 25759108
N1  - Nedoplňovat EF17_043/0009632.
KW  - Parkinson’s disease
KW  - gut inflammation
KW  - inflammatory bowel disease
KW  - α synuclein
KW  - gut–brain axis
UR  - https://pubs.acs.org/doi/full/10.1021/acsptsci.4c00286
N2  - Parkinson’s disease (PD) is not just reflective of synucleinopathies that affect the brain but also the gastrointestinal (GI) tract. (1) The pathological features of PD include the loss of dopaminergic (DAergic) neurons within substantia nigra pars compacta (SNpc), as well as the appearance of intraneuronal inclusions known as Lewy bodies or Lewy neurites, which are primarily composed of self-aggregatory protein α-synuclein (α-syn). (2) Globally, an estimated 6.2 million people are believed to have PD and its prevalence is expected to increase 2.5-fold by 2040. (3) In addition, recent epidemiological research also suggests that PD patients have a variety of prodromal GI dysfunctions, including delayed gastric emptying, infrequent bowel movements, and chronic constipation, decades before they acquire centrally driven motor deficits of PD. (4) Correspondingly, GI tissue of PD patients has shown changes in functional and structural activities during the early stage of the disease, including the presence of α-syn-containing inclusions, impaired mucosal barrier function, and altered bacterial composition. (5,6) The presentation of GI pathology is linked with the Braak hypothesis, which states that ingestion/inhalation of unknown environmental triggers causes the development of α-syn pathology first in the enteric nervous system (ENS), followed by impacted lower brain stem regions, such as the dorsal motor nucleus of the vagus nerve (DMV), locus coeruleus (LC), and subsequently to the SNpc, where it induces death of DAergic neurons. (7) In support of this, several preclinical studies have recently demonstrated transneuronal transfer of injected recombinant α-syn into the gut wall to the brain via the vagal nerve. (8−10) Clinical studies have also revealed that complete truncal vagotomy is now linked to a lower risk of PD. (11) These reports indicate that enteric α-syn pathology can spread from the GI tract to the brain. Still, only a few studies have been conducted to explain the molecular mechanism associated with the development of enteric α-syn pathology and its long-distance upward transmission to the brain.
ER  -

SHARMA, Nishant; Monica SHARMA; Disha THAKKAR; Hemant KUMAR; Soňa SMETANOVÁ; Lucie BUREŠOVÁ; Petr ANDRLA a Amit Suresh KHAIRNAR. Chronic DSS-Induced Colitis Exacerbates Parkinson’s Disease Phenotype and Its Pathological Features Following Intragastric Rotenone Exposure. \textit{ACS PHARMACOLOGY \&{} TRANSLATIONAL SCIENCE}. WASHINGTON: AMER CHEMICAL SOC, 2025, roč.~8, č.~2, s.~346-367. ISSN~2575-9108. Dostupné z: https://doi.org/10.1021/acsptsci.4c00286.

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