Malondialdehyde Mediated Alpha-Synuclein Aggregation: A
Plausible Etiology of Parkinson's Disease in Oxidative Stress

J 2025

Malondialdehyde Mediated Alpha-Synuclein Aggregation: A Plausible Etiology of Parkinson's Disease in Oxidative Stress

THAKKAR, Harsh; Sayan CHATTERJEE; Arvind VERMA; Naveen CHANDRASEKAR; Amit Suresh KHAIRNAR et al.

Základní údaje

Originální název

Malondialdehyde Mediated Alpha-Synuclein Aggregation: A Plausible Etiology of Parkinson's Disease in Oxidative Stress

Autoři

THAKKAR, Harsh; Sayan CHATTERJEE; Arvind VERMA; Naveen CHANDRASEKAR; Amit Suresh KHAIRNAR a Ravi P SHAH

Vydání

CHEMICAL RESEARCH IN TOXICOLOGY, WASHINGTON, AMER CHEMICAL SOC, 2025, 0893-228X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30210 Clinical neurology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.800 v roce 2024

Označené pro přenos do RIV

Ano

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

malondialdehyde; alpha-synuclein aggregation; oxidative stress; Parkinson’s disease; protein aggregation

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 26. 2. 2026 12:31, Mgr. Tereza Miškechová

Anotace

V originále

Malondialdehyde (MDA), a major reactive byproduct of lipid peroxidation, has been implicated in numerous pathological conditions as a result of altering the structure and function of crucial proteins. One such protein is alpha-synuclein (alpha-Syn), which plays a vital role in the pathogenesis of Parkinson's disease (PD). This study investigates the hypothesis that MDA causes structural alterations in alpha-Syn, promoting its aggregation and exacerbating its toxicological effects. In vivo experiments were conducted where MDA and MDA-modified alpha-Syn were injected to the brain of mice. Behavioral assessments were performed to evaluate motor function changes, while immunohistochemistry was employed to examine the extent of alpha-Syn aggregation in brain tissues. An extraction protocol was also developed exquisitely, enabling quantification of modified alpha-Syn from brain tissue. Moreover, 15Nitrogen-labeled alpha-Syn was employed to establish an absolute quantification method on nLC-HRMS/MS. Our findings demonstrate that MDA-induced modifications in alpha-Syn alter its structural properties and also significantly enhance its aggregation propensity, potentially contributing to the neurodegenerative processes observed in PD. The developed model displayed a nonreversible decline in motor function, neurodegeneration, and aggregation of proteins in the brain mimicking the PD conditions. This research provides valuable insights into the molecular mechanisms of PD, emphasizing the role of MDA-modified proteins in the etiology of PD.

Citovat

THAKKAR, Harsh; Sayan CHATTERJEE; Arvind VERMA; Naveen CHANDRASEKAR; Amit Suresh KHAIRNAR a Ravi P SHAH. Malondialdehyde Mediated Alpha-Synuclein Aggregation: A Plausible Etiology of Parkinson's Disease in Oxidative Stress. CHEMICAL RESEARCH IN TOXICOLOGY. WASHINGTON: AMER CHEMICAL SOC, 2025, roč. 38, č. 4, s. 573-582. ISSN 0893-228X. Dostupné z: https://doi.org/10.1021/acs.chemrestox.4c00348.

@article{2556872,
   author = {Thakkar, Harsh and Chatterjee, Sayan and Verma, Arvind and Chandrasekar, Naveen and Khairnar, Amit Suresh and Shah, Ravi P},
   article_location = {WASHINGTON},
   article_number = {4},
   doi = {https://doi.org/10.1021/acs.chemrestox.4c00348},
   keywords = {malondialdehyde; alpha-synuclein aggregation; oxidative stress; Parkinson’s disease; protein aggregation},
   language = {eng},
   issn = {0893-228X},
   journal = {CHEMICAL RESEARCH IN TOXICOLOGY},
   title = {Malondialdehyde Mediated Alpha-Synuclein Aggregation: A Plausible Etiology of Parkinson's Disease in Oxidative Stress},
   url = {https://pubs.acs.org/doi/10.1021/acs.chemrestox.4c00348},
   volume = {38},
   year = {2025}
}

TY  - JOUR
ID  - 2556872
AU  - Thakkar, Harsh - Chatterjee, Sayan - Verma, Arvind - Chandrasekar, Naveen - Khairnar, Amit Suresh - Shah, Ravi P
PY  - 2025
TI  - Malondialdehyde Mediated Alpha-Synuclein Aggregation: A Plausible Etiology of Parkinson's Disease in Oxidative Stress
JF  - CHEMICAL RESEARCH IN TOXICOLOGY
VL  - 38
IS  - 4
SP  - 573-582
EP  - 573-582
PB  - AMER CHEMICAL SOC
SN  - 0893228X
KW  - malondialdehyde
KW  - alpha-synuclein aggregation
KW  - oxidative stress
KW  - Parkinson’s disease
KW  - protein aggregation
UR  - https://pubs.acs.org/doi/10.1021/acs.chemrestox.4c00348
N2  - Malondialdehyde (MDA), a major reactive byproduct of lipid peroxidation, has been implicated in numerous pathological conditions as a result of altering the structure and function of crucial proteins. One such protein is alpha-synuclein (alpha-Syn), which plays a vital role in the pathogenesis of Parkinson's disease (PD). This study investigates the hypothesis that MDA causes structural alterations in alpha-Syn, promoting its aggregation and exacerbating its toxicological effects. In vivo experiments were conducted where MDA and MDA-modified alpha-Syn were injected to the brain of mice. Behavioral assessments were performed to evaluate motor function changes, while immunohistochemistry was employed to examine the extent of alpha-Syn aggregation in brain tissues. An extraction protocol was also developed exquisitely, enabling quantification of modified alpha-Syn from brain tissue. Moreover, 15Nitrogen-labeled alpha-Syn was employed to establish an absolute quantification method on nLC-HRMS/MS. Our findings demonstrate that MDA-induced modifications in alpha-Syn alter its structural properties and also significantly enhance its aggregation propensity, potentially contributing to the neurodegenerative processes observed in PD. The developed model displayed a nonreversible decline in motor function, neurodegeneration, and aggregation of proteins in the brain mimicking the PD conditions. This research provides valuable insights into the molecular mechanisms of PD, emphasizing the role of MDA-modified proteins in the etiology of PD.
ER  -

THAKKAR, Harsh; Sayan CHATTERJEE; Arvind VERMA; Naveen CHANDRASEKAR; Amit Suresh KHAIRNAR a Ravi P SHAH. Malondialdehyde Mediated Alpha-Synuclein Aggregation: A Plausible Etiology of Parkinson's Disease in Oxidative Stress. \textit{CHEMICAL RESEARCH IN TOXICOLOGY}. WASHINGTON: AMER CHEMICAL SOC, 2025, roč.~38, č.~4, s.~573-582. ISSN~0893-228X. Dostupné z: https://doi.org/10.1021/acs.chemrestox.4c00348.

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