Review Paper 7
古川 良明*
生化学 2018 Vol.90 pp.311-319

Original Paper 41
Tanaka G, Yamanaka T, Furukawa Y, Kajimura N, Mitsuoka K and Nukina N*
“Biochemical and morphological classification of disease-associated alpha-synuclein mutants”
Biochemical and Biophysical Research Communications 2018 Vol.508 pp.729-734

Original Paper 40
Fujiwara N*, Wagatsuma M, Oba N, Yoshihara D, Tokuda E, Sakiyama H, Eguchi H, Ichihashi M, Furukawa Y, Inoue T and Suzuki K
“Cu/Zn-Superoxide Dismutase Forms Fibrillar Hydrogels in a pH-Dependent Manner via a Water-rich Extended Intermediate State”
PLOS ONE 2018 Vol.13 e0205090

Original Paper 39
Furukawa Y*, Lim C, Tosha T, Yoshida K, Hagai T, Akiyama S, Watanabe S, Nakagome K and Shiro Y
“Identification of a novel zinc-binding protein, C1orf123, as an interactor with a heavy metal-associated domain”
PLOS ONE 2018 Vol.13 e0204355

We found C1orf123 protein as a new interactor with a copper chaperone protein CCS. This protein has a novel folding pattern, but we still have no idea on what this protein works for in our body. We are very much thankful to Dr. Tosha@RIKEN for X-ray crystallographic analysis of this brand new protein. Actually, we were almost scooped by the other research group: I was very surprised to see that almost the same paper was published several days after our paper came out!!



Original Paper 38
Okuzumi A, Kurosawa M, Hatano T, Takanashi M, Nojiri S, Fukuhara T, Yamanaka T, Miyazaki H, Yoshinaga S, Furukawa Y, Shimogori T, Hattori N and Nukina N*
“Rapid dissemination of alpha-synuclein seeds through neural circuits in an in-vivo prion-like seeding experiment”
Acta Neuropathologica Communications 2018 Vol.6 96

Original Paper 37
Tamaki Y, Shodai A, Morimura T, Hikiami R, Minamiyama S, Ayaki T, Tooyama I, Furukawa Y, Takahashi R and Urushitani M*
“Elimination of TDP-43 inclusions linked to amyotrophic lateral sclerosis by a misfolding-specific intrabody with dual proteolytic signals”
Scientific Reports 2018 Vol.8 6030


Among our five collaborative papers, the paper by Prof. Urushitani @Shiga-medical Univ. is quite impactful. This paper shows the therapeutic potential of the antibody against TDP-43, which seems to play pathogenic roles in ALS. Because of the press release, ALS patients and their family gave me the response to the study. I am a basic scientist and actually not involved in the medical care, so their response is quite important for me. Thanks to this collaborative study with Prof. Urushitani, I learned a lot about the importance of offering information on our research to the society.

Original Paper 36
Tokuda E, Nomura T, Ohara S, Watanabe S, Yamanaka K, Morisaki Y, Misawa H and Furukawa Y*
“A copper-deficient form of mutant Cu/Zn-superoxide dismutase as an early pathological species in amyotrophic lateral sclerosis”
Biochimica et Biophysica Acta – Molecular Basis of Disease 2018 Vol.1864 pp.2119-2130

Our new paper has been published from BBA-Molecular basis of disease. Several groups including us have suggested that the metal binding in SOD1 is very important in maintaining the native structure and that the metal dissociation triggers misfolding of SOD1 in vitro. Our current study for the first time reveals the accumulation of copper-deficient SOD1 in very early stages of ALS. So, the copper-deficient form of SOD1 will be a promising target for developing a cure of the disease.

新しい論文がBBA-Molecular basis of diseaseから発表されました。私たちを含めていくつかの研究グループが、SOD1タンパク質への金属イオン結合が立体構造の形成・保持に重要であることを提案しており、少なくとも試験管内での実験では、金属イオンの解離によってSOD1はミスフォールド(構造異常化)することを報告しています。今回の私たちの研究では、銅イオンを解離したSOD1が、ALSのかなり初期に形成していることを初めて生体内で捉えることに成功しました。つまり、金属イオン解離型のSOD1はALS治療法開発のターゲットになりうることを示唆する研究と言えます。

「銅イオン未結合型SOD1」を特異的に認識する抗体を開発することに成功し、ALSモデルマウスを用いて検証を行った。脊髄(Spinal cord)では、銅イオンを結合していないSOD1が非常に病初期から存在していることがわかる。