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author:

Fu, Deqiang (Fu, Deqiang.) [1] | Liang, Xingyue (Liang, Xingyue.) [2] | Jiang, Yuxuan (Jiang, Yuxuan.) [3] | Liu, Jieping (Liu, Jieping.) [4] | Lin, Xiaosi (Lin, Xiaosi.) [5] | Yang, Quan (Yang, Quan.) [6] | Chen, Xue (Chen, Xue.) [7] | Huang, Ping (Huang, Ping.) [8] | Wang, Wei (Wang, Wei.) [9] | Wu, Wenlin (Wu, Wenlin.) [10]

Indexed by:

Scopus SCIE

Abstract:

Iron is an essential dietary micronutrient for maintaining physiological homeostasis. However, disruption of cerebral iron regulation with the accumulation of iron in different brain structures appears to have a role in the pathogenesis of various neurodegenerative disorders. Studies have reported that autophagy induction could potentially mitigate progression in neurodegenerative diseases with iron deposition, but the relationship between autophagy and iron remains poorly understood. Meanwhile, abnormal autophagy in microglia is closely related to the occurrence of neurodegenerative diseases. Therefore, the effect of iron on microglia autophagy needs to be elaborated. In the present study, we found that iron induces autophagosome accumulation but inhibits its initiation in an Akt-mTOR pathway independent manner. Meanwhile, it caused autophagy flux defects and dysfunction of lysosomes. We also found that iron overload reduced the expression of Rab7, which is an essential protein for the fusion of autophagosomes and lysosomes. These results suggest that iron induces the accumulation of autophagosome in microglia and disrupts the autophagic flux in late stage of autophagy. Therefore, our work provides new insights into the molecular mechanisms of iron neurotoxicity.

Keyword:

Autophagic flux Autophagy Iron Microglia

Community:

  • [ 1 ] [Fu, Deqiang]Fujian Med Univ, Affiliated Hosp 2, Dept Oncol, Quanzhou 362000, Peoples R China
  • [ 2 ] [Liang, Xingyue]Quanzhou Normal Univ, Coll Oceanol & Food Sci, Quanzhou 362000, Peoples R China
  • [ 3 ] [Jiang, Yuxuan]Quanzhou Normal Univ, Coll Oceanol & Food Sci, Quanzhou 362000, Peoples R China
  • [ 4 ] [Liu, Jieping]Quanzhou Normal Univ, Coll Oceanol & Food Sci, Quanzhou 362000, Peoples R China
  • [ 5 ] [Lin, Xiaosi]Quanzhou Normal Univ, Coll Oceanol & Food Sci, Quanzhou 362000, Peoples R China
  • [ 6 ] [Yang, Quan]Quanzhou Normal Univ, Coll Oceanol & Food Sci, Quanzhou 362000, Peoples R China
  • [ 7 ] [Chen, Xue]Quanzhou Normal Univ, Coll Oceanol & Food Sci, Quanzhou 362000, Peoples R China
  • [ 8 ] [Huang, Ping]Quanzhou Normal Univ, Coll Oceanol & Food Sci, Quanzhou 362000, Peoples R China
  • [ 9 ] [Wu, Wenlin]Quanzhou Normal Univ, Coll Oceanol & Food Sci, Quanzhou 362000, Peoples R China
  • [ 10 ] [Liang, Xingyue]Fuzhou Univ, Sch Adv Manufacture, Jinjiang 362251, Peoples R China
  • [ 11 ] [Wu, Wenlin]Fuzhou Univ, Sch Adv Manufacture, Jinjiang 362251, Peoples R China
  • [ 12 ] [Wang, Wei]Minjiang Univ, Inst Oceanog, Fuzhou 350108, Peoples R China

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Source :

FOOD AND CHEMICAL TOXICOLOGY

ISSN: 0278-6915

Year: 2023

Volume: 181

3 . 9

JCR@2023

3 . 9 0 0

JCR@2023

JCR Journal Grade:1

CAS Journal Grade:3

Cited Count:

WoS CC Cited Count:

SCOPUS Cited Count:

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 0

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