ijms-logo

Journal Browser

Journal Browser

Autophagy in the Nervous System

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 4714

Special Issue Editor

Second Department of Internal Medicine, Division of Neurology, University of Fukui, Fukui, Japan
Interests: Alzheimer’s disease; aggregation; tau oligomer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

As neurons age, their survival depends on eliminating a growing burden of damaged, potentially toxic proteins and organelles. This capability declines with aging and disorders. There are two proteolytic systems, the proteasome system and the autophagic–lysosomal system. Senile plaques consist of amyloid β protein (Aβ) and neurofibrillary tangles (NFTs) which, composed of highly phosphorylated tau protein, are pathological hallmarks of Alzheimer's disease (AD). Accumulation of aggregated forms of a synuclein, TDP43, or huntingtin can be the cause of Parkinson’s disease or dementia with Lewy bodies, amyotrophic lateral sclerosis, or Huntington’s disease, respectively.

Autophagy is considered to be one of the main Aβ-eliminating pathways under normal conditions. The ubiquitin proteasomal system may be the primary mechanism to degrade endogenous tau, while aggregated tau does not undergo degradation by the proteasome. Autophagy is involved in the clearance of soluble and aggregated tau and NFT in the cell. Moreover, autophagy activation can reduce the secretion of tau and tau propagation. These facts imply that autophagy activation can be beneficial for AD via clearance of Aβ or tau. In fact, several therapeutic studies have been performed by modulating autophagy, including mTORC1-dependent and -independent autophagy inducers, other autophagy-inducing drugs, and gene therapy, including microRNA. However, it has been reported that Aβ can be produced in autophagy, and Aβ secretion can also be done by autophagy. This Special Issue will offer us precious information regarding autophagy and Aβ or tau, and autophagy and alpha synuclein, TDP43, and huntingtin. Additionally, it may shed light on whether autophagy activation is beneficial for AD and other neurodegenerative disorders causing dementia.

Dr. Tadanori Hamano
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Alzheimer’s disease
  • tau protein
  • amyloid protein
  • autophagy
  • LC3
  • P62
  • alpha-synuclein
  • TDP-43
  • rapamycin
  • mTORC1

Published Papers (2 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

15 pages, 4773 KiB  
Article
Selaginella tamariscina Inhibits Glutamate-Induced Autophagic Cell Death by Activating the PI3K/AKT/mTOR Signaling Pathways
by Yun Hee Jeong, Tae In Kim, You-Chang Oh and Jin Yeul Ma
Int. J. Mol. Sci. 2022, 23(19), 11445; https://doi.org/10.3390/ijms231911445 - 28 Sep 2022
Cited by 7 | Viewed by 1795
Abstract
Glutamate-induced neural toxicity in autophagic neuron death is partially mediated by increased oxidative stress. Therefore, reducing oxidative stress in the brain is critical for treating or preventing neurodegenerative diseases. Selaginella tamariscina is a traditional medicinal plant for treating gastrointestinal bleeding, hematuria, leucorrhea, inflammation, [...] Read more.
Glutamate-induced neural toxicity in autophagic neuron death is partially mediated by increased oxidative stress. Therefore, reducing oxidative stress in the brain is critical for treating or preventing neurodegenerative diseases. Selaginella tamariscina is a traditional medicinal plant for treating gastrointestinal bleeding, hematuria, leucorrhea, inflammation, chronic hepatitis, gout, and hyperuricemia. We investigate the inhibitory effects of Selaginella tamariscina ethanol extract (STE) on neurotoxicity and autophagic cell death in glutamate-exposed HT22 mouse hippocampal cells. STE significantly increased cell viability and mitochondrial membrane potential and decreased the expression of reactive oxygen species, lactate dehydrogenase release, and cell apoptosis in glutamate-exposed HT22 cells. In addition, while glutamate induced the excessive activation of mitophagy, STE attenuated glutamate-induced light chain (LC) 3 II and Beclin-1 expression and increased p62 expression. Furthermore, STE strongly enhanced the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) phosphorylation activation. STE strongly inhibited glutamate-induced autophagy by activating the PI3K/Akt/mTOR signaling pathway. In contrast, the addition of LY294002, a PI3K/Akt inhibitor, remarkably suppressed cell viability and p-Akt and p62 expression, while markedly increasing the expression of LC3 II and Beclin-1. Our findings indicate that autophagy inhibition by activating PI3K/Akt/mTOR phosphorylation levels could be responsible for the neuroprotective effects of STE on glutamate neuronal damage. Full article
(This article belongs to the Special Issue Autophagy in the Nervous System)
Show Figures

Figure 1

21 pages, 12860 KiB  
Article
Clioquinol Decreases Levels of Phosphorylated, Truncated, and Oligomerized Tau Protein
by Gaoping Lin, Feiyan Zhu, Nicholas M. Kanaan, Rei Asano, Norimichi Shirafuji, Hirohito Sasaki, Tomohisa Yamaguchi, Soichi Enomoto, Yoshinori Endo, Asako Ueno, Masamichi Ikawa, Kouji Hayashi, Osamu Yamamura, Shu-Hui Yen, Yasunari Nakamoto and Tadanori Hamano
Int. J. Mol. Sci. 2021, 22(21), 12063; https://doi.org/10.3390/ijms222112063 - 08 Nov 2021
Cited by 10 | Viewed by 2474
Abstract
The neuropathological hallmarks of Alzheimer’s disease (AD) are senile plaques (SPs), which are composed of amyloid β protein (Aβ), and neurofibrillary tangles (NFTs), which consist of highly phosphorylated tau protein. As bio-metal imbalance may be involved in the formation of NFT and SPs, [...] Read more.
The neuropathological hallmarks of Alzheimer’s disease (AD) are senile plaques (SPs), which are composed of amyloid β protein (Aβ), and neurofibrillary tangles (NFTs), which consist of highly phosphorylated tau protein. As bio-metal imbalance may be involved in the formation of NFT and SPs, metal regulation may be a direction for AD treatment. Clioquinol (CQ) is a metal-protein attenuating compound with mild chelating effects for Zn2+ and Cu2+, and CQ can not only detach metals from SPs, but also decrease amyloid aggregation in the brain. Previous studies suggested that Cu2+ induces the hyperphosphorylation of tau. However, the effects of CQ on tau were not fully explored. To examine the effects of CQ on tau metabolism, we used a human neuroblastoma cell line, M1C cells, which express wild-type tau protein (4R0N) via tetracycline-off (TetOff) induction. In a morphological study and ATP assay, up to 10 μM CQ had no effect on cell viability; however, 100 μM CQ had cytotoxic effects. CQ decreased accumulation of Cu+ in the M1C cells (39.4% of the control), and both total and phosphorylated tau protein. It also decreased the activity of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) (37.3% and 60.7% levels of the control, respectively), which are tau kinases. Of note, activation of protein phosphatase 2A (PP2A), which is a tau phosphatase, was also observed after CQ treatment. Fractionation experiments demonstrated a reduction of oligomeric tau in the tris insoluble, sarkosyl soluble fraction by CQ treatment. CQ also decreased caspase-cleaved tau, which accelerated the aggregation of tau protein. CQ activated autophagy and proteasome pathways, which are considered important for the degradation of tau protein. Although further studies are needed to elucidate the mechanisms responsible for the effects of CQ on tau, CQ may shed light on possible AD therapeutics. Full article
(This article belongs to the Special Issue Autophagy in the Nervous System)
Show Figures

Figure 1

Back to TopTop