Department of Neurology, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104-6077, USA.
J Clin Invest. 2011 Dec;121(12):4624-7. doi: 10.1172/JCI60511.
Hereditary neuropathies are common neurological conditions characterized by progressive loss of motor and/or sensory function. There are no effective treatments. Among the many causes of hereditary neuropathies are dominant mutations in serine palmitoyltransferase, long chain base subunit 1 (SPTLC1), which cause hereditary sensory and autonomic neuropathy type 1 (HSAN1). By incorporating L-alanine in place of L-serine, the mutant HSAN1–associated serine palmitoyltransferase generates deoxysphingolipids, which are thought to be neurotoxic. In this issue of the JCI, Garofalo and colleagues report that oral L-serine reverses the accumulation of deoxysphingolipids in humans with HSAN1 and in a transgenic mouse model. As oral L-serine reduces the severity of neuropathy in the mouse model of HSAN1, these data suggest a rational candidate therapy for this devastating condition.
遗传性周围神经病是一种常见的神经系统疾病，其特征是运动和/或感觉功能进行性丧失。目前尚无有效的治疗方法。遗传性周围神经病的许多病因包括丝氨酸棕榈酰转移酶长链基础亚单位 1（SPTLC1）的显性突变，这会导致遗传性感觉和自主神经病 1 型（HSAN1）。通过用 L-丙氨酸取代 L-丝氨酸，突变的 HSAN1 相关丝氨酸棕榈酰转移酶会产生去氧神经鞘脂，据认为这些物质具有神经毒性。在本期 JCI 中，Garofalo 及其同事报告称，口服 L-丝氨酸可逆转 HSAN1 患者和转基因小鼠模型中去氧神经鞘脂的积累。由于口服 L-丝氨酸可降低 HSAN1 小鼠模型中神经病变的严重程度，这些数据表明这是一种针对这种破坏性疾病的合理候选治疗方法。
