Autophagy and mitophagy elements are increased in body fluids of multiple sclerosis-affected individuals

Patergnani, Simone; Castellazzi, Massimiliano; Bonora, Massimo; Marchi, Saverio; Casetta, Ilaria; Pugliatti, Maura; Giorgi, Carlotta; Granieri, Enrico; Pinton, Paolo

doi:10.1136/jnnp-2017-316234

Cited by 59 publications

(48 citation statements)

References 5 publications

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“…In MS and in experimental auto immune encephalomyelitis, an experimental model of MS, upregulation of the protein kinase mTOR has been described, and treatment with rapamycin/sirolimus (an immunosuppressant that inhibits mTOR and conse quently stimulates macroautophagy) ameliorates some clinical and histological signs of the disease 131 . Increased levels of macroautophagy markers were measured in the blood and brain of patients with MS 122,132 . However, impaired macroautophagy was found in the spinal cord of experimental autoimmune encephalomyelitis mice 133 .…”

Section: Neurological Autoimmune Diseasesmentioning

confidence: 99%

Lysosomes as a therapeutic target

Bonam

Wang

Muller

2019

Nat Rev Drug Discov

495

374

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| Lysosomes are membrane-bound organelles with roles in processes involved in degrading and recycling cellular waste, cellular signalling and energy metabolism. Defects in genes encoding lysosomal proteins cause lysosomal storage disorders, in which enzyme replacement therapy has proved successful. Growing evidence also implicates roles for lysosomal dysfunction in more common diseases including inflammatory and autoimmune disorders, neurodegenerative diseases, cancer and metabolic disorders. With a focus on lysosomal dysfunction in autoimmune disorders and neurodegenerative diseases -including lupus, rheumatoid arthritis, multiple sclerosis, Alzheimer disease and Parkinson disease -this Review critically analyses progress and opportunities for therapeutically targeting lysosomal proteins and processes, particularly with small molecules and peptide drugs.

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Section: Neurological Autoimmune Diseasesmentioning

confidence: 99%

Lysosomes as a therapeutic target

Bonam

Wang

Muller

2019

Nat Rev Drug Discov

495

374

View full text Add to dashboard Cite

show abstract

“…Furthermore, designing autophagy detection kits for non-invasive samples such as plasma or liquid biopsies instead of tissue markers will facilitate less invasive sampling. Interestingly, in patients with multiple sclerosis, the levels of ATG5 and Parkin in the serum and the cerebrospinal fluid were found to be significantly higher than in the control cohorts [190,191]. In addition serum levels of Beclin-1 are related to the stage of diabetic kidney disease and inversely correlate with a kidney dysfunction marker albuminuria in these patients [192].…”

Section: Gathering New Knowledge and Tools For A Better Autophagy Assmentioning

confidence: 96%

Assessing Autophagy in Archived Tissue or How to Capture Autophagic Flux from a Tissue Snapshot

Humbert

Morán

Cruz‐Ojeda

et al. 2020

Biology

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Autophagy is a highly conserved degradation mechanism that is essential for maintaining cellular homeostasis. In human disease, autophagy pathways are frequently deregulated and there is immense interest in targeting autophagy for therapeutic approaches. Accordingly, there is a need to determine autophagic activity in human tissues, an endeavor that is hampered by the fact that autophagy is characterized by the flux of substrates whereas histology informs only about amounts and localization of substrates and regulators at a single timepoint. Despite this challenging task, considerable progress in establishing markers of autophagy has been made in recent years. The importance of establishing clear-cut autophagy markers that can be used for tissue analysis cannot be underestimated. In this review, we attempt to summarize known techniques to quantify autophagy in human tissue and their drawbacks. Furthermore, we provide some recommendations that should be taken into consideration to improve the reliability and the interpretation of autophagy biomarkers in human tissue samples.

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“…Moreover, they have been demonstrated that level of TNF-α, an inflammation marker, escalated in MS individuals, suggesting that autophagic activity and inflammation may be correlate each other. It is concluded that, with continue of investigations, serum levels of these autophagic/mitophagic molecules could be used as a diagnostic or progression biomarkers of MS [54]. Meanwhile, in other study, Igci et al probed autophagy-related genetic profile of MS individuals and observed that many autophagyrelated genes significantly over expressed in MS patients compared to healthy controls, including ULK1, ULK2, FOXO1, Bcl-2, Htt, UVRAG, Atg2B, Atg4C, Atg5, TMEM74, DAPK1, EIF2AK3, Atg11, p62, PIK3R1.…”

Section: Protective Role Of Autophagy In Msmentioning

confidence: 99%

Real-state of autophagy signaling pathway in neurodegenerative disease; focus on multiple sclerosis

et al. 2020

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The occurrence of neurodegenerative disease is increasingly raised. From physiopathological aspect, the emergence of auto-reactive antibodies against the nervous system antigens contributes to de-myelination in Multiple sclerosis (MS). These features cause the nervous system dysfunction. The follow-up of molecular alterations could give us a real-state vision about intracellular status during pathological circumstances. In this review, we focus on the autophagic response during MS progression and further understand the relationship between autophagy and MS and its modulatory effect on the MS evolution. The authors reviewed studies published on the autophagy status in neurodegenerative disease and on the autophagy modulation in MS prognosis, diagnosis, and possible therapies. The inevitable role of autophagy was shown in the early-stage progression of MS. Due to critical role of autophagy in different stage of cell activity in nervous system, the distinct role of autophagy should not be neglected in the development, pathogenesis, and treatment of MS.

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Autophagy and mitophagy elements are increased in body fluids of multiple sclerosis-affected individuals

Cited by 59 publications

References 5 publications

Lysosomes as a therapeutic target

Lysosomes as a therapeutic target

Assessing Autophagy in Archived Tissue or How to Capture Autophagic Flux from a Tissue Snapshot

Real-state of autophagy signaling pathway in neurodegenerative disease; focus on multiple sclerosis

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