Protein LYRIC

Protein LYRIC (MTDH) is a 63 kDa multifunctional protein that modulates transcriptional and cellular processes involved in tumor biology and metastasis (UniProt: Q86UE4). It down-regulates the SLC1A2/EAAT2 glutamate transporter promoter, activates NF-κB signaling, and promotes anchorage-independent growth and metastatic spread to multiple organs including the brain. The protein also induces chemoresistance in cancer cells, suggesting roles in both oncogenic and stress-response pathways.

MTDH expression and function intersect with neurobiological processes, particularly glutamate homeostasis through EAAT2 regulation, which is relevant to neurotoxicity and neuroinflammation. No specific Alzheimer's Disease mutations or associations are documented in the UniProt entry, though the protein's role in NF-κB activation connects to inflammatory signaling implicated in neurodegeneration.

MTDH is upregulated in Alzheimer's Disease brain tissue relative to age-matched controls (mean log2 fold-change: +0.373; Chaparral AD proteomics). This elevation was detected across post-mortem AD brain samples analyzed by mass spectrometry, suggesting a potential contribution to AD-associated pathology through enhanced NF-κB signaling and altered glutamate transporter regulation.