Our Research
Exploring the Epigenetic Features of ALS/FTD
ALS is a progressive neurodegenerative disease that affects both lower motor neurons in the brainstem and spinal cord, and the upper motor neurons in the motor cortex. ALS often occurs concurrently with frontotemporal dementia (FTD), another disorder involving progressive neuronal loss. ALS and FTD form a neurodegenerative continuum and share pathological and genetic features. No cure is available for ALS/FTD, and current treatments fail to control symptoms. ALS/FTD is classified into two categories: familial and sporadic, both of which present with similar clinical symptoms; ALS/FTD has been linked to mutations in 40 different genes. How can so many genes—involving many distinct cellular functions—produce the same symptomatology? And how can we treat a disease with so many apparent molecular causes? Could there be a role for epigenetics in the etiology of ALS/FTD?
Eukaryotic DNA is packaged into chromatin, a highly organized protein-DNA complex. Changes in the composition and structure of chromatin are sufficient to cause heritable phenotypic changes. These changes are termed epigenetic. Epigenetics determines whether, when, and how particular genes will be transcribed. The basic unit of chromatin is the nucleosome, which consists of DNA wrapped around a histone core. The N-terminal "tails" of histones project out of the nucleosome core. The protruding histone tails are decorated with various post-translational modifications (PTMs) including chemical moieties such as phosphorylation, methylation, and acetylation. These modifications regulate access to genetic information. We hypothesize that epigenetic mechanisms—namely histone modifications—play a pivotal role in the neuronal death characterizing ALS/FTD. Our lab studies the histone modification profiles relating to ALS/FTD in several model systems using both immunoblotting and proteomic methods.