Correlation between auto/mitophagic processes and magnetic resonance imaging activity in multiple sclerosis patients.
Autophagy
Biomarkers
Magnetic resonance imaging
Mitophagy
Multiple sclerosis
Journal
Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974
Informations de publication
Date de publication:
27 Jun 2019
27 Jun 2019
Historique:
received:
18
02
2019
accepted:
19
06
2019
entrez:
29
6
2019
pubmed:
30
6
2019
medline:
7
1
2020
Statut:
epublish
Résumé
An alteration of autophagy and mitophagy, two highly conserved lysosome-dependent degradation pathways involved in the maintenance of cellular homeostasis, has been associated with multiple sclerosis (MS). To search the level of autophagy-related 5 (ATG5) and Parkin proteins, as markers of autophagy and mitophagy respectively, and lactate in a cohort of MS patients. Cerebrospinal fluid (CSF) and serum samples from 60 MS patients were analyzed: 30 with magnetic resonance imaging (MRI) evidence of disease activity, gadolinium (Gd)-based contrast agent positive (Gd+), and 30 without MRI evidence of disease activity (Gd-). ATG5, Parkin, and lactate were measured using commercially available products. Serum levels of ATG5, Parkin, and lactate were more elevated in Gd+ than in Gd- MS patients (p < 0.0001), and CSF concentrations of ATG5 and Parkin were greater in Gd+ than in Gd- MS (p < 0.0001). Our results demonstrated that molecular markers of autophagy and mitophagy are increased in CSF of MS patients during the active phases of the disease and that these catabolic markers, together with lactate, are also remarkably augmented in blood suggesting a role of these processes in MS pathogenesis and the possible use of these molecules as biomarkers of disease activity.
Sections du résumé
BACKGROUND
BACKGROUND
An alteration of autophagy and mitophagy, two highly conserved lysosome-dependent degradation pathways involved in the maintenance of cellular homeostasis, has been associated with multiple sclerosis (MS).
OBJECTIVE
OBJECTIVE
To search the level of autophagy-related 5 (ATG5) and Parkin proteins, as markers of autophagy and mitophagy respectively, and lactate in a cohort of MS patients.
METHODS
METHODS
Cerebrospinal fluid (CSF) and serum samples from 60 MS patients were analyzed: 30 with magnetic resonance imaging (MRI) evidence of disease activity, gadolinium (Gd)-based contrast agent positive (Gd+), and 30 without MRI evidence of disease activity (Gd-). ATG5, Parkin, and lactate were measured using commercially available products.
RESULTS AND CONCLUSIONS
CONCLUSIONS
Serum levels of ATG5, Parkin, and lactate were more elevated in Gd+ than in Gd- MS patients (p < 0.0001), and CSF concentrations of ATG5 and Parkin were greater in Gd+ than in Gd- MS (p < 0.0001). Our results demonstrated that molecular markers of autophagy and mitophagy are increased in CSF of MS patients during the active phases of the disease and that these catabolic markers, together with lactate, are also remarkably augmented in blood suggesting a role of these processes in MS pathogenesis and the possible use of these molecules as biomarkers of disease activity.
Identifiants
pubmed: 31248423
doi: 10.1186/s12974-019-1526-0
pii: 10.1186/s12974-019-1526-0
pmc: PMC6598368
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
131Subventions
Organisme : Fondazione Telethon
ID : GGP15219/B
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : IG-18624
Organisme : Associazione Italiana per la Ricerca sul Cancro
ID : IG-19803
Organisme : Italian Ministry of Health
ID : GR-2013-02356747
Organisme : Fondazione Cariplo
ID : NA
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