Chaperone-Mediated Autophagy in Neurodegenerative Diseases and Acute Neurological Insults in the Central Nervous System

Kanno, Haruo; Handa, Kyoichi; Murakami, Taishi; Aizawa, Tadanori; Ozawa, Hiroshi

doi:10.3390/cells11071205

Cited by 28 publications

(15 citation statements)

References 153 publications

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“…Thus, autophagy activation is recently emerging as a hot topic to study neuroprotective mechanisms in chronic retinal neurodegenerative disorders (Kaarniranta et al, 2022). Similarly, given the parallelism between traumatic and chronic degenerative conditions, the activation of autophagy in the course of traumatic CNS injury is thought to produce a strong activation to elicit functional and anatomical recovery (Movahedpour et al, 2022;Zhang et al, 2022;Filippone et al, 2022;Xu et al, 2022;Kanno et al, 2022). This is partly based on the induction of stem cells (Xu et al, 2021;Maiti et al, 2019;Ceccariglia et al, 2020;Hwang et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Combined pulses of light and sound in the retina with nutraceuticals may enhance the recovery of foveal holes

Pinelli¹,

Berti²,

Scaffidi³

et al. 2022

Archives Italiennes De Biologie

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The present manuscript stems from evidence, which indicates that specific wavelength produce an activation of the autophagy pathway in the retina. These effects were recently reported to synergize with the autophagy-inducing properties of specific phytochemicals. The combined administration of photo-modulation and phytochemicals was recently shown to have a strong potential in eliciting the recovery in the course of retinal degeneration and it was suggested as a non-invasive approach named "Lugano protocol" to treat age-related macular degeneration (AMD). Recent translational findings indicate that the protective role of autophagy may extend also to acute neuronal injuries including traumatic neuronal damage. At the same time, very recent investigations indicate that autophagy activation and retinal anatomical recovery may benefit from sound exposure. Therefore, in the present study, the anatomical rescue of a traumatic neuronal loss at macular level was investigated in a patient with idiopathic macular hole by using a combined approach of physical and chemical non-invasive treatments. In detail, light exposure was administered in combination with sound pulses to the affected retina. This treatment was supplemented by phytochemicals known to act as autophagy inducers, which were administered orally for 6 months. This combined administration of light and sound with nutraceuticals reported here as Advanced Lugano's Protocol (ALP) produced a remarkable effect in the anatomical architecture of the retina affected by the macular hole. The anatomical recovery was almost complete at roughly one year after diagnosis and beginning of treatment. The structural healing of the macular hole was concomitant with a strong improvement of visual acuity and the disappearance of metamorphopsia. The present findings are discussed in the light of a synergism shown at neuronal level between light and sound in the presence of phytochemicals to stimulate autophagy and promote proliferation and neuronal differentiation of retinal stem cells.

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Section: Introductionmentioning

confidence: 99%

Combined pulses of light and sound in the retina with nutraceuticals may enhance the recovery of foveal holes

Pinelli¹,

Berti²,

Scaffidi³

et al. 2022

Archives Italiennes De Biologie

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“…Previous studies have also indicated that chaperon-mediated autophagy (CMA), which is inhibited by RARα, is activated by BT382 without inhibiting macroautophagy ( Anguiano et al, 2013 ; Gomez-Sintes et al, 2022 ). CMA activation, which shows neuroprotection in neurodegenerative diseases and acute neurological insults ( Cuervo and Wong, 2014 ; Kanno et al, 2022 ), may be related to the neuroprotective effects of BT382 against P7 ethanol toxicity. Presently, we have not studied the long-term effects of BT382, partly because we expect that once initial apoptotic neurodegeneration is blocked, subsequent glial activation and GABAergic cell loss would be also blocked, as indicated in our previous studies using lithium ( Sadrian et al, 2012 ; Lewin et al, 2018 ; Saito et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of retinoic acid receptor α modulators on developmental ethanol-induced neurodegeneration and neuroinflammation

et al. 2023

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Ethanol exposure in neonatal mice induces acute neurodegeneration followed by long-lasting glial activation and GABAergic cell deficits along with behavioral abnormalities, providing a third trimester model of fetal alcohol spectrum disorders (FASD). Retinoic acid (RA), the active form of vitamin A, regulates transcription of RA-responsive genes and plays essential roles in the development of embryos and their CNS. Ethanol has been shown to disturb RA metabolism and signaling in the developing brain, which may be a cause of ethanol toxicity leading to FASD. Using an agonist and an antagonist specific to RA receptor α (RARα), we studied how RA/RARα signaling affects acute and long-lasting neurodegeneration and activation of phagocytic cells and astrocytes caused by ethanol administered to neonatal mice. We found that an RARα antagonist (BT382) administered 30 min before ethanol injection into postnatal day 7 (P7) mice partially blocked acute neurodegeneration as well as elevation of CD68-positive phagocytic cells in the same brain area. While an RARα agonist (BT75) did not affect acute neurodegeneration, BT75 given either before or after ethanol administration ameliorated long-lasting astrocyte activation and GABAergic cell deficits in certain brain regions. Our studies using Nkx2.1-Cre;Ai9 mice, in which major GABAergic neurons and their progenitors in the cortex and the hippocampus are labeled with constitutively expressed tdTomato fluorescent protein, indicate that the long-lasting GABAergic cell deficits are mainly caused by P7 ethanol-induced initial neurodegeneration. However, the partial reduction of prolonged GABAergic cell deficits and glial activation by post-ethanol BT75 treatment suggests that, in addition to the initial cell death, there may be delayed cell death or disturbed development of GABAergic cells, which is partially rescued by BT75. Since RARα agonists including BT75 have been shown to exert anti-inflammatory effects, BT75 may rescue GABAergic cell deficits by reducing glial activation/neuroinflammation.

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“…Autophagy plays a major role in many diseases, including immune diseases [ 35 , 36 ], neurodegenerative diseases [ 37 ], atherosclerosis [ 38 ], and cancers [ 39 , 40 ]. Our present work suggests that autophagy may also have a role in eosinophilic asthma.…”

Section: Discussionmentioning

confidence: 99%

Autophagy Protects against Eosinophil Cytolysis and Release of DNA

Esnault

Fichtinger

Barretto

et al. 2022

Cells

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The presence of eosinophils in the airway is associated with asthma severity and risk of exacerbations. Eosinophils deposit their damaging products in airway tissue, likely by degranulation and cytolysis. We previously showed that priming blood eosinophils with IL3 strongly increased their cytolysis on aggregated IgG. Conversely, IL5 priming did not result in significant eosinophil cytolysis in the same condition. Therefore, to identify critical events protecting eosinophils from cell cytolysis, we examined the differential intracellular events between IL5- and IL3-primed eosinophils interacting with IgG. We showed that both IL3 and IL5 priming increased the eosinophil adhesion to IgG, phosphorylation of p38, and production of reactive oxygen species (ROS), and decreased the phosphorylation of cofilin. However, autophagic flux as measured by the quantification of SQSTM1-p62 and lipidated-MAP1L3CB over time on IgG, with or without bafilomycin-A1, was higher in IL5-primed compared to IL3-primed eosinophils. In addition, treatment with bafilomycin-A1, an inhibitor of granule acidification and autophagolysosome formation, enhanced eosinophil cytolysis and DNA trap formation in IL5-primed eosinophils. Therefore, this study suggests that increased autophagy in eosinophils protects from cytolysis and the release of DNA, and thus limits the discharge of damaging intracellular eosinophilic contents.

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Chaperone-Mediated Autophagy in Neurodegenerative Diseases and Acute Neurological Insults in the Central Nervous System

Cited by 28 publications

References 153 publications

Combined pulses of light and sound in the retina with nutraceuticals may enhance the recovery of foveal holes

Combined pulses of light and sound in the retina with nutraceuticals may enhance the recovery of foveal holes

Effects of retinoic acid receptor α modulators on developmental ethanol-induced neurodegeneration and neuroinflammation

Autophagy Protects against Eosinophil Cytolysis and Release of DNA

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