Volume 7 Issue 4 • 1000358 J Alzheimers Dis Parkinsonism, an open access journal ISSN:2161-0460 Open Access Research Article Sugimoto et al., J Alzheimers Dis Parkinsonism 2017, 7:4 DOI: 10.4172/2161-0460.1000358 Journal of Alzheimer’s Disease & Parkinsonism J o u r n a l o f A l z h e i m e r s D i s e a s e & P a r k i n s o n i s m ISSN: 2161-0460 *Corresponding author: Hiwasa T, Department of Biochemistry and Genetics, Chiba University, Graduate School of Medicine, Japan, Tel: 81432262541; E-mail: hiwasa_takaki@faculty.chiba-u.jp Received July 14, 2017; Accepted July 27, 2017; Published August 03, 2017 Citation: Sugimoto K, Tomiyoshi G, Mori M, Kuwabara S, Hirano S, et al. (2017) Identifcation of Serum Anti-GADD34 Antibody as a Common Marker of Diabetes Mellitus and Parkinson Disease. J Alzheimers Dis Parkinsonism 7: 358. doi: 10.4172/2161-0460.1000358 Copyright: © 2017 Sugimoto K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Keywords: GADD34; PPP1R15A; Parkinson disease; Diabetes mellitus; Serum antibody biomarker Abbreviations: ABI, ankle-branchial index; aCI, acute-phase cerebral infarction; ALB, albumin; AlphaLISA, amplifed luminescence proximity homogeneous assay-linked immunosorbent assay; ALS, amyotrophic lateral sclerosis; AST, aspartate aminotransferase; ATF4, activating transcription factor 4; Atg12, autophagy 12; ATP2B4, ATPase, Ca ++ - transporting, plasma membrane 4; AUC, area under the ROC curve; BMI, body mass index; BMP-1, bone morphogenetic protein 1; CAVI, cardio-ankle vascular index; CHOP, C/EBP homologous protein; CI, confdence interval; CKD, chronic kidney disease; CRE, creatinine; CVD, cardiovascular disease; DHPS, deoxyhypusine synthase; DM, diabetes mellitus; ECSA, esophageal carcinoma SEREX antigen; ER, endoplasmic reticulum; E. coli, Escherichia coli; GAD65, 65kDa form of glutamic acid decarboxylase; GADD3, growth arrest and DNA-damage-inducible gene 34; GST, glutathione-S-transferase; Hb, hemoglobin; HbA1c, glycated hemoglobin; HD, healthy donor; HDL-C, high-density lipoprotein cholesterol; Hsp, heat shock protein; IA-2, insulinoma antigen 2; LDL-C, low-density lipoprotein cholesterol; LRRK2, leucine- rich repeat kinase 2; max IMT, maximum intima-media thickness; PD, Parkinson disease; PERK, protein kinase RNA-like endoplasmic reticulum kinase; PINK1, PTEN-induced putative kinase 1; PRKN, parkin RBR E3 ubiquitin protein ligase; ROC, receiver operating curve; RPA2, replication protein A2; SD, standard deviation; SEREX, serological identifcation of antigens by recombinant cDNA expression cloning; SH3BP5, SH3 domain-binding protein 5; SH3GL1, SH3-domain GRB2- like 1; s-GADD34-Abs, serum anti-GADD34 antibodies; SNCA, α-synuclein; SOSTDC1, sclerostin domain-containing protein 1; TACSTD2, tumor-associated calcium signal transducer 2; TRIM21, tripartite motif-containing 21; TUBB2C, tubulin beta-2C; ZnT8, zinc transporter 8. Introduction Parkinson disease (PD) is a common neurodegenerative disease with core pathological features including progressive dopaminergic Abstract Background: Growth arrest and DNA-damage-inducible gene 34 (GADD34) has been identifed as an antigen by serological identifcation of antigens by cDNA expression cloning (SEREX) using the sera of patients with atherosclerosis. It is possible that GADD34 is associated with atherosclerosis-related diseases such as diabetes mellitus (DM), acute-phase cerebral infarction (aCI), cardiovascular disease (CVD), and chronic kidney disease (CKD) as well as endoplasmic reticulum stress-related Parkinson disease (PD). Methods: GADD34 protein was bacterially expressed and purifed. Amplifed luminescent proximity homogeneous assay (AlphaLISA) was used to evaluate serum antibody levels against GADD34 protein in serum samples. Results: AlphaLISA revealed signifcantly higher serum antibody levels against GADD34 protein in patients with DM, aCI and CVD than those in healthy donors (HDs). The difference in levels between DM and HD was more prominent than that between aCI or CVD and HDs. The anti-GADD34 antibody levels were also elevated in the sera of diabetic CKD patients; thus, the anti-GADD34 antibodies appeared to be the most associated with DM, which is also a risk factor of PD. Anti-GADD34 antibody levels were also higher in patients with PD but not in those with amyotrophic lateral sclerosis as compared with those in HDs. Conclusion: Anti-GADD34 antibody may be a useful diagnostic tool for DM and PD. GADD34 may account for the pathophysiological relationship between DM and PD. Identification of Serum Anti-GADD34 Antibody as a Common Marker of Diabetes Mellitus and Parkinson Disease Kazuo Sugimoto 1,2,# , Go Tomiyoshi 2,3,# , Masahiro Mori 1 , Satoshi Kuwabara 1 , Shigeki Hirano 1 , Setsu Sawai 1 , Minako Beppu 1,4 , Mayumi Muto 1 , Akiyuki Uzawa 1 , Kenichiro Kitamura 5 , Minoru Takemoto 6 , Akiko Hattori 6 , Masashi Yamamoto 6 , Kazuki Kobayashi 6 , Harukiyo Kawamura 6 , Ryoichi Ishibashi 6 , Koutaro Yokote 6 , Seiichiro Mine 7,8,9 , Toshio Machida 9 , Eiichi Kobayashi 7 , Yoichi Yoshida 7 , Tomoo Matsutani 7 , Yasuo Iwadate 7 , Yoshio Kobayashi 10 , Rika Nakamura 2,3 , Natsuko Shinmen 2,3 , Hideyuki Kuroda 3 , Hao Wang 2,11 , Xiao-Meng Zhang 2 and Takaki Hiwasa 2 * 1 Department of Neurology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan 2 Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan 3 Medical Project Division, Research Development Center, Fujikura Kasei Co., Saitama 340-0203, Japan 4 Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan 5 Department of Internal Medicine 3, University of Yamanashi School of Medicine, Yamanashi 409-3898, Japan 6 Department of Clinical Cell Biology and Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan 7 Department of Neurological Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan 8 Department of Neurological Surgery, Chiba Prefectural Sawara Hospital, Chiba 287-0003, Japan 9 Department of Neurological Surgery, Chiba Cerebral and Cardiovascular Center, Chiba 290-0512, Japan 10 Department of Cardiovascular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan 11 Department of Anesthesia, The First Affliated Hospital, Jinan University, Guangzhou 510630, P. R. China Ϯ Authors contributed equally