Autophagopathies: from autophagy gene polymorphisms to precision medicine for human diseases

Grosjean, Iris; Roméo, Barnabé; Domdom, Marie Angela; Belaïd, Amine; D’Andréa, Gregoire; Guillot, Nicolas; Gherardi, Romain K.; Gal, Jocelyn; Milano, Gérard; Marquette, Charles-Hugo; Hung, Rayjean J.; Landi, Maria Teresa; Han, Younghun; Brest, Patrick; Bergen, Martin von; Klionsky, Daniel J.; Amos, Christopher I.; Hofman, Paul; Mograbi, Baharia

doi:10.1080/15548627.2022.2039994

Cited by 21 publications

(18 citation statements)

References 194 publications

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“…In terms of achieving a balance of disease/control participant demographics, our findings and observations from other groups support the position that chronological age informs (and is influence by), the state of the biochemical processes that regulate autophagy ( Table 1 ; [27, 29, 30]). This is demonstrated in COPD, where accelerated senescence and unscheduled apoptosis are hallmarks of disease and are associated with the dysregulation of autophagy [3, 31-33]. While our evaluation of autophagy remained significant after correcting for the age disparity, assessments using homogenous participant groups will be a central prerequisite leading to a diagnostic model that is predictive of COPD.…”

Section: Discussion/conclusionmentioning

confidence: 90%

Autophagy is suppressed in peripheral blood mononuclear cells during chronic obstructive pulmonary disease

Cooper,

Chen,

Lester

et al. 2024

Preprint

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Assessing autophagy promises to provide valuable information regarding the pathogenesis of chronic obstructive pulmonary disease (COPD). However, measuring the dynamic aspect of autophagy is challenging, and sample manipulation can cause signal fluctuations that deviate from the situation in vivo. Our aim was to assess an organotypic method to quantify autophagy in the context of COPD, where autophagy has demonstrated disease-related modulation. Blood from control and COPD participants was treated with/out chloroquine. Protein from peripheral blood mononuclear cells (PBMC) was then isolated and compared for LC3B-II abundance. Our observations show that while basal level LC3B-II abundance was similar between each group (P = 0.60), autophagic flux was significantly lower in the COPD cohort, suggesting disruption in autophagy (P = 0.004). We aim to extend this inquiry and compare pulmonary vs blood samples, to identify the utility of measuring autophagy in blood as a diagnostic outcome predictive of early COPD.

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Section: Discussion/conclusionmentioning

confidence: 90%

Autophagy is suppressed in peripheral blood mononuclear cells during chronic obstructive pulmonary disease

Cooper,

Chen,

Lester

et al. 2024

Preprint

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“…CLEC16A has been found to play a role in the regulation of autophagy, an evolutionarily conserved process by which cells break down and recycle damaged or dysfunctional cellular components [3]. Autophagy is important for maintaining cellular homeostasis, and dysregulation of this process has been implicated in various diseases, including neurodegeneration, cancer, metabolic disorders, and autoimmunity [106][107][108]. Based on degraded cell components, some selective types of autophagy identified are mitophagy, ribophagy, reticulophagy, lysophagy, pexophagy, lipophagy, and glycophagy [106].…”

Section: Clec16a In Health and Diseases Through Gwasmentioning

confidence: 99%

CLEC16A—An Emerging Master Regulator of Autoimmunity and Neurodegeneration

Pandey

Bakay

Hákonarson

2023

IJMS

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CLEC16A is emerging as an important genetic risk factor for several autoimmune disorders and for Parkinson disease (PD), opening new avenues for translational research and therapeutic devel-opment. While the exact role of CLEC16A in health and disease is still being elucidated, the gene plays a critical role in the regulation of autophagy, mitophagy, endocytosis, intracellular trafficking, immune function, and in biological processes such as insulin secretion and others that are important to cellular homeostasis. As shown in both human and animal modeling studies, CLEC16A hypo-function predisposes to both autoinflammatory phenotype and neurodegeneration. While the two are clearly related, further functional studies are needed to fully understand the mechanisms in-volved for optimized therapeutic interventions. Based on recent data, mitophagy-inducing drugs may be warranted, and such therapy should be tested in clinical trials as these drugs would tackle the underlying pathogenic mechanism (s) and could treat or prevent symptoms of autoimmunity and neurodegeneration in individuals with CLEC16A risk variants. Accordingly, interventions di-rected at reversing the dysregulated mitophagy and the consequences of loss of function of CLEC16A without activating other detrimental cellular pathways could present an effective ther-apy. This review presents the emerging role of CLEC16A in health and disease and provides an update on the disease processes that are attributed to variants located in the CLEC16A gene, which are responsible for autoimmune disorders and neurodegeneration with emphasis on how this in-formation is being translated into practical and effective applications in the clinic.

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“…The progression of this process is facilitated by a group of proteins encoded by ATG, as depicted in Figure 1. The intricate molecular mechanisms underlying autophagy are extensively discussed in other expert reviews 25 …”

Section: Autophagy and Related Molecular Pathwaysmentioning

confidence: 99%

“…The intricate molecular mechanisms underlying autophagy are extensively discussed in other expert reviews. 25 Although macro-, micro-, and chaperone-mediated autophagy are all considered to be genuine forms of autophagy, as they transport cytoplasmic materials to lysosomes, 26 recent research has revealed noncanonical autophagy pathways. These pathways are called noncanonical autophagy because they use distinct molecular pathways to process and conjugate microtubuleassociated protein light chain 3 (LC3).…”

Section: Autophagy and Related Molecular Pathwaysmentioning

confidence: 99%

Modulation of the immunity and inflammation by autophagy

Gan

Zhang

et al. 2023

MedComm

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Autophagy, a highly conserved cellular self‐degradation pathway, has emerged with novel roles in the realms of immunity and inflammation. Genome‐wide association studies have unveiled a correlation between genetic variations in autophagy‐related genes and heightened susceptibility to autoimmune and inflammatory diseases. Subsequently, substantial progress has been made in unraveling the intricate involvement of autophagy in immunity and inflammation through functional studies. The autophagy pathway plays a crucial role in both innate and adaptive immunity, encompassing various key functions such as pathogen clearance, antigen processing and presentation, cytokine production, and lymphocyte differentiation and survival. Recent research has identified novel approaches in which the autophagy pathway and its associated proteins modulate the immune response, including noncanonical autophagy. This review provides an overview of the latest advancements in understanding the regulation of immunity and inflammation through autophagy. It summarizes the genetic associations between variants in autophagy‐related genes and a range of autoimmune and inflammatory diseases, while also examining studies utilizing transgenic animal models to uncover the in vivo functions of autophagy. Furthermore, the review delves into the mechanisms by which autophagy dysregulation contributes to the development of three common autoimmune and inflammatory diseases and highlights the potential for autophagy‐targeted therapies.

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Autophagopathies: from autophagy gene polymorphisms to precision medicine for human diseases

Cited by 21 publications

References 194 publications

Autophagy is suppressed in peripheral blood mononuclear cells during chronic obstructive pulmonary disease

Autophagy is suppressed in peripheral blood mononuclear cells during chronic obstructive pulmonary disease

CLEC16A—An Emerging Master Regulator of Autoimmunity and Neurodegeneration

Modulation of the immunity and inflammation by autophagy

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