Lafora disease: Current biology and therapeutic approaches.
Lafora disease: Current biology and therapeutic approaches.
复制标题
DOI：
10.1016/j.neurol.2021.06.006
复制
发表时间：
2022-04
影响因子：
3
通讯作者：
Minassian BA
中科院分区：
文献类型：
--
作者：
Mitra S;Gumusgoz E;Minassian BA
The ubiquitin system impacts most cellular processes and is altered in numerous neurodegenerative diseases. However, little is known about its role in neurodegenerative diseases due to disturbances of glycogen metabolism such as Lafora disease (LD). In LD, insufficiently branched and long-chained glycogen forms and precipitates into insoluble polyglucosan bodies (Lafora bodies), which drive neuroinflammation, neurodegeneration and epilepsy. LD is caused by mutations in the gene encoding the glycogen phosphatase laforin or the gene coding for the laforin interacting partner ubiquitin E3 ligase malin. The role of the malin-laforin complex in regulating glycogen structure remains with full of gaps. In this review we bring together the disparate body of data on these two proteins and propose a mechanistic hypothesis of the disease in which malin-laforin’s role to monitor and prevent over-elongation of glycogen branch chains, which drive glycogen molecules to precipitate and accumulate into Lafora bodies. We also review proposed connections between Lafora bodies and the ensuing neuroinflammation, neurodegeneration and intractable epilepsy. Finally, we review the exciting activities in developing therapies for Lafora disease based on replacing the missing genes, slowing the enzyme - glycogen synthase - that over-elongates glycogen branches, and introducing enzymes that can digest Lafora bodies. Much more work is needed to fill the gaps in glycogen metabolism in which laforin and malin operate. However, knowledge appears already adequate to advance disease course altering therapies for this catastrophic fatal disease.
登录
查看更多内容
Lafora病小鼠模型中的结构和功能性脑异常。
影响因子：
5.6
作者：
Burgos DF;Cussó L;Sánchez-Elexpuru G;Calle D;Perpinyà MB;Desco M;Serratosa JM;Sánchez MP
通讯作者：
Sánchez MP
影响因子：
3.5
作者：
Aguado C;Sarkar S;Korolchuk VI;Criado O;Vernia S;Boya P;Sanz P;de Córdoba SR;Knecht E;Rubinsztein DC
通讯作者：
Rubinsztein DC
影响因子：
5.1
作者：
Berthier A;Payá M;García-Cabrero AM;Ballester MI;Heredia M;Serratosa JM;Sánchez MP;Sanz P
通讯作者：
Sanz P
影响因子：
14.5
作者：
Ahonen, Saija;Nitschke, Silvia;Minassian, Berge A.
通讯作者：
Minassian, Berge A.
影响因子：
6.2
作者：
Augé E;Pelegrí C;Manich G;Cabezón I;Guinovart JJ;Duran J;Vilaplana J
通讯作者：
Vilaplana J