■Familial cerebellar ataxia caused by CBLN1 gene mutation and molecular therapy using AAV (Molecular Therapy) 2026.8.15 Yamasaki T, Kakegawa W, Hayashi A., Ogawa N, Takano T, Matsuda K, Takatsuto K, Abdel-Hamid MS, Zaki MS, Gleeson J, Yuzaki M. AAV-mediated CBLN1 replacement rescues hereditary ataxia caused by biallelic CBLN1 variants. Mol Ther. 2026 Sep 2:S1525-0016(26)00772-0. doi: 10.1016/j.ymthe.2026.09.003. Epub ahead of print. PMID: 42687380.
In this research、We report two families with recessive cerebellar ataxia caused by point mutations in CBLN1.、By creating a mouse model, we clarified the pathology and molecular mechanism.。In addition, adeno-associated virus (AAV))By expressing CBLN1 in glial cells using、Even in adult animals that have already developed cerebellar ataxia, we have shown that it restores cerebellar synapses and ameliorates ataxic symptoms.。

■Tmem178 connects two major presynaptic hub proteins, Neurexin and PTPR (Nature Commun) 2026.8.15 Thivaios S, swivel J, Brechet A, With Boudkkazi, Sethumadhavan N, Henneken P, Miura E, Hayashi A., Kocylowski MK, Main A, Kaminski D, Schreiner D, Nowacka A, van den Broucke JB, Kulik A, Schulte U, Sterky FH, Yuzaki M, Scheiffele P, Torches B. Ternary Neurexin-T178-PTPR complexes represent a pre-synaptic core-module of neuronal synapse organization. Nat Commun. 2026 Sep 5;17(1):9509. doi: 10.1038/s41467-026-77377-4. PMID: 42701130.
In this research、Various proteins accumulate at the presynaptic region, which is the point of contact between nerve cells.、Neurexin (Nrx), a “hub protein” that controls synapse formation and differentiation)Focused on、We comprehensively identified proteins that bind to Nrx by immunoprecipitation followed by mass spectrometry.。Of the identified membrane proteins、Darkness178 (T178)teeth、At the same time as Nrx, receptor tyrosine dephosphorylase (PTPR))It was found that it combines with。Until now, it has been used as a hub protein in the presynaptic region to control synapse formation and maturation.、Although Nrx and PTPR were known、How these molecules work together has been a mystery.。Tmem178 is it、Through the formation of a tripartite complex called Nrx-T178-PTPR、We revealed that it plays a role in connecting these two hub proteins.。In yuzu 﨑研、To increase the specificity of immunoprecipitation and immunostaining、Mr. Hayashi created various epitope tag knock-in mice.、Mr. Miura then conducted a localization analysis of Tmem178 using these knock-in mice.。

■New properties of neuroligin, a protein that connects nerve cells, revealed (Biochem Biophys Res Commun) 2026.6.25 Uto Y, Yokoo T, Yuzaki M, Tsumoto K, Nakado M. Mass photometry analysis revealed monomer-dimer equilibrium of the synaptic adhesion molecule neuroligin. Biochem Biophys Res Commun. 2026 June 25;819:153830. doi: 10.1016/j.bbrc.2026.153830. Epub 2026 Apr 22. PMID: 42033941. In this research、We focused on neuroligin, a protein that is important for the formation of synapses, which are the points of contact between nerve cells.。Neuroligin is、2It has been thought that the two molecules act as a dimer.、It was not fully understood how stable that bond was.。Therefore, using a new measurement technology called mass photometry,、human neuroligin 1、2、3We have analyzed in detail。as a result、Neuroligins do not always exist as dimers;、It has been revealed that the state of one molecule and the state of two molecules bonded dynamically go back and forth depending on the concentration.。Also、The ease of forming dimers differs depending on the type of neuroligin.、Neuroligin 3 forms the strongest dimer、Then Neuroligin 2、It was found that the order of neuroligin 1。This result is、This provides new clues to understanding how synapses form and mature.。This is a research paper by Uto, a graduate student at the University of Tokyo Tsumoto Laboratory and Nakakido Laboratory.。