Neurochemistry Lab

About Neurochemistry Lab

Our laboratory has one of the longest histories in Japan for biochemical and pharmacological research on neuropsychiatric disorders.
We are pursuing the search for the causes and treatments of dementia and other psychiatric disorders by analyzing them from various perspectives using biochemical methods and state-of-the-art techniques. Visits are always welcome. Please get in touch with the person in charge using the contact details below.

Main research topics

Pathological significance of nucleic acid repeat expansion in neuropsychiatric disorders

The advent of new-generation sequencers and advances in in silico analysis technology have made it possible to decipher genome sequences that could not be solved before. A number of diseases caused by the repetitive and abnormal extension of specific sequences in the genome have been discovered.

Most of these repetitive sequences are not recognized as protein-coding sequences. Still, it is now known that they are translated into disease-related proteins by an unusual mechanism.

In some cases of inherited frontotemporal dementia, the disease is caused by an unusual expansion of the six-base repeat sequence GGGGCC in the untranslated region of the C9ORF72 gene, and those with this repeat sequence are known to have a high frequency of psychotic symptoms.

Kohji Mori, in our laboratory, has previously shown that this repeat sequence is, in fact, translated into repeat proteins and that they accumulate in large amounts in patient brains. Similarly, neuronal inclusion body disease is known to show an unusual expansion of three bases, GGC, in the gene NOTCH2NLC, which causes various symptoms, including dementia.

Similar repeat sequence expansions have been found one after another in autism spectrum disorders and schizophrenia.

We are conducting molecular research into the mechanism by which these abnormal sequences cause neuropsychiatric disorders.

Blood and CSF biomarker development for neuropsychiatric disorders

Currently, the only CSF biomarkers that have also been found to be clinically valuable in dementia are the 'Aβ42/Aβ40 ratio' and 'phosphorylated (pT181) tau' in Alzheimer's disease and the 'abnormal prion' in Creutzfeldt-Jakob disease. There are no established CSF biomarkers for other dementing diseases or blood biomarkers.

However, various candidate biomarkers are emerging in the research field. At the vanguard of these are 'neurofilament light chain' and 'phosphorylated tau (pT181, pT217)', which can be measured in blood. Our laboratory is measuring these in real patient samples and examining their clinical usefulness. In addition, research is being conducted to isolate and analyze extracellular vesicles (some of which are also called exosomes) in blood and CSF to use them as new biomarkers.

Furthermore, we are participating in developing national guidelines for adequately using cerebrospinal fluid and blood biomarkers and APOE testing for dementia.

Conference presentations, paper presentations, and study abroad

We actively encourage our postgraduate students to present at international conferences. (For the latest information, see News (Japanese page) ).

To date, many of our postgraduates have gone on to study at research institutions abroad (e.g., in the USA and Germany). We also accept international students from abroad, both as postgraduate students and in research positions.

We are accepting visitors

If you are interested in our laboratory, please do not hesitate to contact our office (wafukai@psy.med.osaka-u.ac.jp). We are always looking forward to hearing from you.

Representative works

For more information, please see the member's Researchmap website.

  • Mori K, Shigenobu K, Beck G, Uozumi R, Satake Y, Suzuki M, Kondo S, Gotoh S, Yonenobu Y, Kawai M, Suzuki Y, Saito Y, Morii E, Hasegawa M, Mochizuki H, Murayama S, Ikeda M. A heterozygous splicing variant IVS9-7A>T in intron 9 of the MAPT gene in a patient with right-temporal variant frontotemporal dementia with atypical 4 repeat tauopathy Acta Neuropathologica Communications 11 (1), 130, 2023
  • Mori K, Gotoh S, Yamashita T, Uozumi R, Kawabe Y, Tagami S, Kamp F, Nuscher B, Edbauer D, Haass C, Nagai Y, Ikeda M The porphyrin TMPyP4 inhibits elongation during the non-canonical translation of the FTLD/ALS-associated GGGGCC repeat in the C9orf72 gene Journal of Biological Chemistry 297(4) 101120, 2021
  • Akamine S, Marutani N, Kanayama D, Gotoh S, Maruyama R, Yanagida K, Sakagami Y, Mori K, Adachi H, Kozawa J, Maeda N, Otsuki M, Matsuoka T, Iwahashi H, Shimomura I, Ikeda M, Kudo T. Renal Function is Associated with Blood Neurofilament Light Chain Level in Older Adults Scientific Reports 10:20350, 2020
  • Kawabe Y, Mori K, Yamashita T, Gotoh S, Ikeda M. The RNA exosome complex degrades expanded hexanucleotide repeat RNA in C9orf72 FTLD/ALS. The EMBO Journal 39(19):e102700, 2020
  • Mori K, Nihei Y, Arzberger T, Zhou Q, Mackenzie I.R., Herrmann A, Hanisch F, German Consortium for Frontotemporal Lobar Degeneration, Bavarian Brain Banking Alliance, Kamp F, Nuscher B, Orozco D, Edbauer D and Haass C*: Reduced hnRNPA3 increases C9orf72 repeat RNA levels and dipeptide-repeat protein deposition. EMBO Reports 17, 1314-1325, 2016.
  • Mori K, Weng SM, Arzberger T, Rentzsch K, Kremmer E, Schmid B, Kretzschmar HA, Cruts M, van Broeckhoven C, Haass C, Edbauer D: The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS. SCIENCE 339(6125): 1335-1338, 2013