NEFL in the Progression of Alzheimer's Disease through the TSC1-mTOR Signaling Pathway

Lihua WU; Minli YAN; Tian MENG; Yongsheng HE; Ruina LIU

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Lihua WU, Minli YAN, Tian MENG, Yongsheng HE, Ruina LIU. NEFL in the Progression of Alzheimer's Disease through the TSC1-mTOR Signaling Pathway[J]. Journal of Kunming Medical University.

Citation:

Lihua WU, Minli YAN, Tian MENG, Yongsheng HE, Ruina LIU. NEFL in the Progression of Alzheimer's Disease through the TSC1-mTOR Signaling Pathway[J]. Journal of Kunming Medical University.

Lihua WU, Minli YAN, Tian MENG, Yongsheng HE, Ruina LIU. NEFL in the Progression of Alzheimer's Disease through the TSC1-mTOR Signaling Pathway[J]. Journal of Kunming Medical University.

Citation:

Lihua WU, Minli YAN, Tian MENG, Yongsheng HE, Ruina LIU. NEFL in the Progression of Alzheimer's Disease through the TSC1-mTOR Signaling Pathway[J]. Journal of Kunming Medical University.

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NEFL in the Progression of Alzheimer's Disease through the TSC1-mTOR Signaling Pathway

1.
Department of Medical Rehabilitation Center，Taiyuan Social Children’s Welfare Institute，Taiyuan Shanxi 030027
2.
Department of Neurosurgery，Shanxi Provincial People’s Hospital，Taiyuan Shanxi 030000
3.
Department of Project Management，Yunnan Yunke Institute of Biotechnology，Kunming Yunnan 650500，China

Received Date: 2025-12-09
Available Online: 2026-07-27

Abstract

Abstract

Objective To investigate the potential mechanism by which neurofilament light chain （NEFL） affects the progression of Alzheimer’ s disease （AD） through its interaction with tuberous sclerosis complex 1 （TSC1）. Methods An AD model was established in adult male Sprague-Dawley rats by streptozotocin（STZ）injection. An in vitro cell model was established by treating neuronal cells with amyloid β peptide 1–42 （Aβ_1–42）. Cognitive and motor functions were evaluated by the novel object recognition test and the rotarod test. The expression of NEFL and TSC1 were detected by RT-qPCR. The protein expression of NEFL, TSC1, p-TSC1, mTOR, p-mTOR, S6K1, and p-S6K1 were detected by western blot. The cell viability was detected by CCK-8 kit. The contents of IL-6, IL-1β, TNF-α, Aβ_1-42, and p-Tau in cells and tissues were detected by ELISA kits. The levels of GSH, MDA, SOD, and AChE in cells and tissues were detected by biochemical kits. The apoptosis rates was detected by flow cytometry. Co-immunoprecipitation assay was used to detect the interaction between NEFL and TSC1. Results An AD rat model was successfully established. The expression of NEFL was markedly upregulated in the hippocampal tissue of AD rats, while TSC1 expression markedly downregulated. NEFL knockdown alleviated cognitive and motor dysfunction in AD rats, reduced inflammatory responses and oxidative stress injury in hippocampal tissues, and inhibited the protein expression of p-mTOR and p-S6K1 (P < 0.05). In Aβ_1-42-induced neurons, NEFL expression was markedly increased (P < 0.0001), while TSC1 expression was markedly decreased (P < 0.0001). After NEFL knockdown, TSC1 expression was significantly increased (P < 0.0001), cell apoptosis rate was significantly reduced (P < 0.0001), and cell viability was significantly restored (P < 0.0001). NEFL knockdown also suppressed the levels of IL-1β, IL-6, and TNF-α induced by Aβ_1-42 (P < 0.0001), suppressed the elevation of MDA and AChE (P < 0.0001), and increased the levels of GSH and SOD (P < 0.01). Compared with the sh-NC group, the protein expression levels of p-mTOR and p-S6K1 (P < 0.001) were significantly downregulated in the sh-NEFL group. Co-immunoprecipitation results showed that NEFL interacted with TSC1. Knockdown of NEFL upregulated the protein expression of TSC1 and p-TSC1 (P < 0.01), whereas overexpression of TSC1 inhibited NEFL protein expression (P < 0.05). Moreover, knockdown of TSC1 reversed the effects of NEFL knockdown. Conclusion Knockdown of NEFL not only can alleviate inflammatory response and improve oxidative stress state, but also may exert neuroprotective effects by inhibiting the mTOR/S6K1 signaling pathway.
- Alzheimer’ s disease,
- neurofilament light chain,
- tuberous sclerosis complex 1

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References(22)

References

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