MDM2 in the signaling pathways related to neurological diseases

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• Mouse double minute 2 homolog (MDM2) is a key regulator of the p53 pathway, controlling cell cycle, DNA damage response, and apoptosis.
• Emerging evidence highlights MDM2's non-canonical functions in the central nervous system (CNS), implicating it in neurodegenerative diseases, brain injury, neuroinflammation, and cognitive dysfunction.

Purpose of the Study:

• To review the multifaceted, non-canonical roles of MDM2 in CNS disorders.
• To establish a stage- and cell-type-specific framework for MDM2 regulation within the CNS.
• To introduce a therapeutic-window concept for balancing neuroprotection and adaptive stress responses.

Main Methods:

• Literature review integrating current advances on MDM2 in CNS disorders.
• Focus on MDM2's involvement in mitochondrial homeostasis, autophagy, synaptic plasticity, immune modulation, and metabolic signaling.
• Distinguishing p53-dependent and p53-independent pathways regulated by MDM2.

Main Results:

• MDM2 plays diverse roles in the CNS beyond its oncogenic functions.
• MDM2 is implicated in the pathogenesis and progression of various neurological conditions.
• A framework distinguishing p53-dependent and -independent MDM2 functions in the CNS is presented.

Conclusions:

• MDM2 acts as a dynamic molecular switch influencing neuronal fate.
• Understanding context-specific MDM2 regulation is crucial for neurological disease therapeutics.
• MDM2 offers potential for developing targeted therapeutic strategies in neurological disorders.