In recent years, the beneficial effects of curcumin (CUR) have been widely demonstrated in experimental and clinical studies. This natural polyphenol protects against toxic agents acting on the human body, including the nervous system. In particular, CUR has been investigated for its multiple biological effects mostly focusing on autophagy activation, which is considered particularly relevant to counteract various toxicants and disease conditions. In detail, the present study, we specifically challenged the protective efficacy of CUR on METH-induced toxicity based on the molecular events triggered by METH, which consist in profound alterations in the autophagy machinery. These effects were investigated in a catecholamine-containing cell line, namely the rat pheochromocytoma PC12 cell line. This latter was chosen as unbiased, low variable in vitro model to test the pro-autophagic activity of CUR. In such a system, a strong protection was exerted by CUR against METH toxicity. This was associated with increased autophagy flux, merging of autophagy and lysosomal proteins and re-allocation of LC3 inside the autophagy vacuoles, which instead is dispersed by METH. This is expected to enable the autophagy machinery. Under the effects of CUR, LC3 increases within autophagy vacuoles to commit them to cell clearance and promotes the autophagy flux. This is in line with the evidence that in METH-treated PC12 cells α-synuclein accumulates within the cytosol, whereas CUR promotes the clearance of this autophagy substrate. The present data provide evidence that CUR induces neuroprotection against METH toxicity by promoting the autophagy pathway.

AUTOPHAGY-BASED EFFECTS OF CURCUMIN IN METH-INDUCED TOXICITY

Morucci G
Primo
;
Lazzeri G;Natale G;Ferrucci M
Penultimo
;
Fornai F
Ultimo
2021

Abstract

In recent years, the beneficial effects of curcumin (CUR) have been widely demonstrated in experimental and clinical studies. This natural polyphenol protects against toxic agents acting on the human body, including the nervous system. In particular, CUR has been investigated for its multiple biological effects mostly focusing on autophagy activation, which is considered particularly relevant to counteract various toxicants and disease conditions. In detail, the present study, we specifically challenged the protective efficacy of CUR on METH-induced toxicity based on the molecular events triggered by METH, which consist in profound alterations in the autophagy machinery. These effects were investigated in a catecholamine-containing cell line, namely the rat pheochromocytoma PC12 cell line. This latter was chosen as unbiased, low variable in vitro model to test the pro-autophagic activity of CUR. In such a system, a strong protection was exerted by CUR against METH toxicity. This was associated with increased autophagy flux, merging of autophagy and lysosomal proteins and re-allocation of LC3 inside the autophagy vacuoles, which instead is dispersed by METH. This is expected to enable the autophagy machinery. Under the effects of CUR, LC3 increases within autophagy vacuoles to commit them to cell clearance and promotes the autophagy flux. This is in line with the evidence that in METH-treated PC12 cells α-synuclein accumulates within the cytosol, whereas CUR promotes the clearance of this autophagy substrate. The present data provide evidence that CUR induces neuroprotection against METH toxicity by promoting the autophagy pathway.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1117105
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