NEFL Participates 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 Participates 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 Participates 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 Participates in the Progression of Alzheimer's Disease through the TSC1-mTOR Signaling Pathway[J]. Journal of Kunming Medical University.

Citation:

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NEFL Participates 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

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. Cognitive and motor functions were evaluated using the novel object recognition test and the rotarod test. An in vitro cell model was established by treating neuronal cells with amyloid β peptide 1–42 （Aβ_1–42）. RT-qPCR was used to detect the expression of NEFL and TSC1. Western blot was used to detect the expression levels of NEFL, TSC1, p-TSC1, mTOR, p-mTOR, S6K1, and p-S6K1 proteins. The CCK-8 kit was used to detect cell viability. ELISA kit was used to detect the contents of IL-6, IL-1β, TNF-α, Aβ1-42, and p-Tau in cells and tissues. Biochemical kits were used to detect the levels of GSH, MDA, SOD, and AChE in cells and tissues. Flow cytometry was used to detect the apoptosis rates. 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 significantly upregulated in the hippocampal tissue of AD rats, while TSC1 expression was significantly downregulated. Knockdown of NEFL 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 Aβ1-42-induced neurons, NEFL expression was significantly increased （P < 0.0001）, while TSC1 expression was significantly 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 decreased the levels of IL-1β, IL-6, and TNF-α induced by Aβ1-42 （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 an interaction between NEFL and 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 alleviates inflammatory response and improves oxidative stress status, but may also exert neuroprotective effects by inhibiting the mTOR/S6K1 signaling pathway.
- Alzheimer’ s disease,
- NEFL,
- TSC1,
- Neuroinflammation,
- Oxidative stress

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References(22)

References

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