LINE-1 activation in the cerebellum drives ataxia
Takahashi T, Stoiljkovic M, Song E, Gao XB, Yasumoto Y, Kudo E, Carvalho F, Kong Y, Park A, Shanabrough M, Szigeti-Buck K, Liu ZW, Kristant A, Zhang Y, Sulkowski P, Glazer PM, Kaczmarek LK, Horvath TL, Iwasaki A. LINE-1 activation in the cerebellum drives ataxia. Neuron 2022, 110: 3278-3287.e8. PMID: 36070749, PMCID: PMC9588660, DOI: 10.1016/j.neuron.2022.08.011.Peer-Reviewed Original ResearchConceptsLINE-1 activationL1 activationAtaxia telangiectasia patientsNuclear element-1Transposable elementsEpigenetic silencersHuman genomeL1 promoterMolecular regulatorsDNA damagePurkinje cell dysfunctionElement 1First direct evidenceTelangiectasia patientsDirect targetingCerebellar expressionNeurodegenerative diseasesDisease etiologyCalcium homeostasisUVB-mediated DNA damage induces matrix metalloproteinases to promote photoaging in an AhR- and SP1-dependent manner
Kim DJ, Iwasaki A, Chien AL, Kang S. UVB-mediated DNA damage induces matrix metalloproteinases to promote photoaging in an AhR- and SP1-dependent manner. JCI Insight 2022, 7: e156344. PMID: 35316219, PMCID: PMC9090247, DOI: 10.1172/jci.insight.156344.Peer-Reviewed Original ResearchConceptsSpecificity protein 1DNA damageSp1-dependent mannerProtein 1Activator protein-1HaCaT human immortalized keratinocytesExtracellular matrix componentsTranscription factorsAryl hydrocarbon receptorHuman immortalized keratinocytesMatrix componentsHydrocarbon receptorPotential targetImmortalized keratinocytesROSSun-exposed skinType IV collagenMMP2 expressionAhRMatrix metalloproteinasesMechanistic studiesMMP2IV collagenTopical treatmentMMP-1