Aberrant protein kinases and phosphoproteins in amyotrophic lateral sclerosis

作者：Krieger C^*; Hu JH; Pelech S

来源：Trends in Pharmacological Sciences, 2003, 24(10): 535-541.

DOI：10.1016/j.tips.2003.08.003

Amyotrophic lateral sclerosis (ALS) is a human neurological disorder that results in progressive weakness and, ultimately, death. Although mutations in the SOD1 gene are found occasionally in ALS patients, there is no evidence of a heritable trait in the vast majority of ALS patients. Furthermore, variability is observed in the clinical presentation of ALS, raising the possibility that ALS is a heterogeneous disorder. In this article, we propose that several distinct initiating factors for ALS, including mutations in SOD1, trigger a common cascade of 'downstream' processes that result in neuronal death. Several studies demonstrate that abnormal expression or activities of protein kinases are common in ALS, and we hypothesize that some of these changes contribute to neuronal death. Phosphorylation of neuron-specific substrates can alter the binding and physiological properties of the substrate and might lead to neurotoxicity.

• 出版日期2003-10