Telomerase expression in amyotrophic lateral sclerosis (ALS) patients

Abstract

Telomerase and telomeric complex have been linked to a variety of disease states related to neurological dysfunction. In amyotrophic lateral sclerosis (ALS) patients, telomerase activity, as human telomerase reverse transcriptase (hTERT) expression, has not been characterized yet. Here, for the first time, we characterized telomerase and related pathway in blood sample and spinal cord from ALS patients compared with healthy controls. We found that hTERT expression level was significantly lower in ALS patients and was correlated either to p53 mRNA expression or p21 expression, pointing out the hypothesis that telomerase inhibition could be a pathogenetic contributor to neurodegeneration in ALS. As a consequence of the reduced telomerase activity, we identified shorter telomeres in leukocytes from sporadic ALS patients compared with healthy control group.

Telomere shortening leads to earlier age of onset in ALS mice

“…However, there are also studies reporting no such association in PD [ 50 , 51 ]. Moreover, a recent study demonstrates decreased expression of human telomerase reverse transcriptase (hTERT) in leukocytes of ALS patients and consequently shorter telomeres in ALS leukocytes [ 40 ]. In contrast, we found a trend for increased telomere length in microglia in the brains of ALS patients.…”

“…We found that telomerase knockout resulting in telomere shortening is capable of reducing survival and acceleration of ALS disease onset in SOD1 G93A mice. Interestingly, a decrease of hTERT expression leading to reduced telomerase activity was recently reported in post-mortem spinal cord of ALS patients compared to healthy controls [ 40 ]. Low levels of hTERT in mature neurons might contribute to their vulnerability of various oxidative insults [ 58 , 59 ].…”

“…Due to the severity of the disease and missing therapeutic options, pathological psychological stress often accompanies ALS [ 37 - 39 ]. Interestingly, a recent study identified shorter telomeres in leukocytes from sporadic ALS patients compared with healthy controls [ 40 ]. However, telomere length especially in human ALS brains has not been characterized yet.…”

“…Therefore telomerase knockout mice (mTerc −/− ) provide an elegant experimental system to study aging induced by telomere dysfunction and DNA damage [ 42 - 44 ]. Interestingly, a strong reduction in telomerase expression in spinal cord of sporadic ALS patients could be observed compared to healthy controls [ 40 ].…”

Senataxin: A Putative RNA: DNA Helicase Mutated in ALS4—Emerging Mechanisms of Genome Stability in Motor Neurons

“…Telomerase reverse Senataxin: A Putative RNA: DNA Helicase Mutated in ALS4-Emerging Mechanisms… DOI: http://dx.doi.org/10.5772/intechopen.90215 transcriptase (TERT), the catalytic subunit of telomerase that maintains the normal length of telomeres, is present at a low level in most differentiated cells including neurons [106]. TERT levels appear to be significantly lower in the spinal cord tissues of ALS patients than healthy individuals [107]. Ex vivo studies have suggested that while telomere damage induces neuronal cell death [108], the activation of telomerase can enhance neuronal cell viability [109,110].…”