miR-124 regulates cell apoptosis and autophagy in dopaminergic neurons and protects them by regulating AMPK/mTOR

Xin Gong1, Huiqing Wang2, Yongyi Ye2

  • 1Department of Neurosurgery, Zhujiang Hospital, Southern Medical University; The National Key Clinical Specialty, The Engineering Technology Research Center of Education Ministry of China, Guangdong Provincial Key Laboratory on Brain Function Repair and RegenerationGuangzhou 510282, Guangdong, China; Department of Neurosurgery, Hunan Provincial People's HospitalChangsha 410005, Hunan, China.

Insights

MicroRNA-124 (miR-124) protects dopaminergic neurons in Parkinson's disease (PD) by regulating apoptosis and autophagy. Its suppression increases neuronal death and alters autophagy, while restoration offers protection via the AMPK/mTOR pathway.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • MicroRNA-124 (miR-124) is increasingly recognized for its roles in disease development.
  • Parkinson's disease (PD) involves dopaminergic (DA) neuronal loss, apoptosis, and altered autophagy.
  • Understanding miR-124's function in PD pathogenesis is crucial.

Purpose of the Study:

  • To investigate the role of miR-124 in DA neuronal apoptosis and autophagy in PD.
  • To explore the underlying molecular mechanisms involving the AMPK/mTOR pathway.

Main Methods:

  • MPTP-treated human SH-SY5Y cells were used as a PD model.
  • RT-PCR and western blotting analyzed miR-124 mRNA, apoptosis, autophagy markers (Beclin 1, LC3 II/LC3 I), and AMPK/mTOR pathway proteins.
  • miR-124 levels were manipulated using vector transfection.

Main Results:

  • MPTP treatment downregulated miR-124 in neurons.
  • miR-124 suppression increased DA neuronal apoptosis and induced autophagy.
  • Restoring miR-124 decreased apoptosis and normalized autophagy markers.
  • miR-124 suppression altered the AMPK/mTOR pathway, increasing p-AMPK and decreasing p-mTOR.

Conclusions:

  • miR-124 acts as a protective factor for DA neurons in PD.
  • Its protective effects are mediated through the regulation of apoptosis and autophagy.
  • The AMPK/mTOR pathway is a key mechanism through which miR-124 exerts its neuroprotective functions in PD.

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.0K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.2K
Parkinson's Disease: Treatment01:24

Parkinson's Disease: Treatment

Neurodegenerative disorders, such as Parkinson's Disease (PD), involve the gradual and irreversible destruction of neurons in particular brain areas. These disorders exhibit standard features like proteinopathies, selective vulnerability of some neurons, and an interaction of intrinsic properties, genetics, and environmental influences in neural injury.
Parkinson's Disease is primarily a result of the loss of dopaminergic neurons in the substantia nigra pars compacta. The cornerstone of...
1.3K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
9.1K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
6.0K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
4.9K