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Healthy Aging Research Center

 

 

 

Neurodegenerative Diseases

Neurodegenerative Diseases Research Team

 

PI: Jin-Chung Chen, Ph. D

Research Expertise: Parkinson's Disease, Depression, Drug Addiction

 

Team members

 Dr. Jin-Chung Chen, Ph.D.; Dr. Chin-Song Lu, M.D.; Dr. Hung-Li Wang, Ph.D., Dr. Chun-Mao Yang, Ph.D.; Dr. Ing-Tsung Hsiao, Ph.D.; Dr. Jiun-Jie Wang, Ph.D.; Dr. Chien Chou, Ph.D.; Dr. Rong-Chi Huang, Ph.D.; Dr. Guo-Jen Huang, Ph.D.

 

Conceptual Framework

 

 

General description

The goal of Division of Neurodegenerative Diseases, HARC is to advance our current knowledge and explore novel biomarkers and bio-signature in neurodegenerative diseases, in particular two major ageing diseases in the central nervous system, i.e. Parkinson’s disease (PD) and Alzheimer’s disease (AD). The AD and PD represents the leading two neurodegenerative diseases world-wide. Based on the statistics, more than 200 billion medical-related capital costs were spent on AD/PD in USA and it is in general believed the figure will be increasing providing lifespan prolongs. In Taiwan, the patients in AD/PD and other neurodegenerative diseases will expect to be doubled in next 20 years, reaching 200-300 thousands. Hence, understanding the etiology of neural degeneration, mechanism of disease progress or identifying early diagnostic biomarker(s) or bio-signature would be essential to combat the AD/PD or other neurodegenerative disease in order to cut-down the social cost and enhance our welfare. 

 

Background

Both PD and AD have familial and idiopathic causes, with the latter outnumbers the former. Since the discovery of the diseases during early twenty century, there are multiple factors known to contribute individually or in combination the progress of PD or AD. The similarity between PD and AD is the feature of abnormal protein aggregation in particular brain region, i.e. b-amyloid deposits and abnormal tau-protein phosphorylation in AD and Lewy body formation of the PD. So far, there are AD1-AD4 genes (amyloid precursor protein [APP], apolipoprotein E4, presinillin 1 and 2) encoded protein targets/risk factor that would contribute to the pathological phenotypes of the AD, eventually display explicit clinic symptoms includes the hallmark amnesia. Except the standard acetylcholinesterase inhibitor (tarcrine and donepezil) or nootropics, pharmacological therapeutics against AD are rather limited. As for PD, once the disease was simply characterized by the loss of neurotransmitter dopamine in the striatum (nucleus caudate and putamen), thus characteristic movement disorder and resting tremor make sense of the designated functions for dopamine and post-synaptic acetylcholine neurons in this brain region. Medication via dopaminergic strategy thus is the pharmacological mainstay against PD, however suffered with profound side effects (dyskinesia and on-off syndrome) after chronic use. With advances in knowledge of PD, there are PARK1-PARK14 genes now are known to contribute the disease progress, ultimately disrupt the striatal dopamine function and cause motion deficit. With the help of molecular tools plus the specific neurotoxin, various genetic engineered mice or toxin-treated animals were validated for animal models in PD/AD. The success of knock-out or transgenic approaches not only facilitates the understanding of disease progress but provides a useful platform for potential drug screening or gene therapy on novel target(s). In addition, the use of advanced technique such as induced pluripotent stem cell (iPS), one could de-differentiate the diseased neuronal cells into progenitor/stem phenotypes for mechanistic study. Group in neurodegenerative diseases, HARC will adopt various aspects of advanced knowledge in PD and AD to form program project, apply cutting edge technology (piggyBac iPS, genomic, next-generation sequencing, proteomic, molecular imaging and metabolomics) for systemic and molecular approaches.

Taking advantage of extensive resources in Chang-Gung clinical sector and creditable research teams in both Chang-Gung University and Memorial Hospital (Physiology and Pharmacology, Neurology, Neurosurgery, Psychiatry and Nuclear Medicine), our ultimate goal is to bridge the novel clinic findings with basic research and verify in unique model systems, i.e. cell line or animal models. For these purposes, we propose several key research topics to be addressed and the establishment of essential research platforms to cope with our research attempts. The basic structure of research platforms for neurodegenerative diseases study will be served for (a) acquisition of massive database obtained from genomic, proteomic and metabolomics approaches, and (b) evaluation the database (either domestic collected or international collaboration) through various in vivo and in vitro models for ultimate systemic integration.

 

 Aims

The specific aims of neurodegenerative disease research group in HARC are to provide molecular and cellular mechanism of key regulators that are known to participate the neuropathogenesis of PD, AD and other neurodegenerative diseases. Based on the extensive experience of the PIs in different area of neuroscience, we will apply multiple aspects of research and approach from systemic to cellular. In addition, we will collaborate in an intimate research team to generate a framework analysis in order to achieve high profile research results. In this regards, we will apply various animal and cellular models to pinpoint important questions and provide in-depth mechanisms from molecular, cellular to behavioral level. The proposed research studies fall into some major areas, i.e. PD, AD and neuroinflammation-related diseases/disorders. Our research team will collaborate intimately with clinical team in Chang-Gung Memorial Hospital, in particular Neuroscience Research Center (NRC) for sharing the database and creating unique transgenic, knonck-in, knock-out mice or piggyBac iPS cell line based on human genetic analyses from familial PD patients.

 

Methods

(1) Biomarker and Bio-signature identification: The importance of early diagnostic biomarkers or risk factor identification reflects not only in cost and effectiveness of clinical treatment, but the successiveness of disease curability. In both PD and AD, there are approximately 10-15% of the causes belongs to nonfamilial type in contrast to 85% of idiopathic (or familial type). Both genetic biomarkers and risk factors would determine the progress and fate of neural degeneration. Considering these two factors are partly could be universal, while significant parts are influenced by local environmental factors and family gene traces, it is essential to establish the domestic biobank to strengthen our research competitiveness around the world. Taking advantage of CGMH available biobank that includes the collection from cerebrospinal fluid (CSF), serum, urine or autopsy brain tissues from PD/AD and other neurodegenerative disease patients, in addition to normal age-matched healthy controls, analyzed samples are well-organized and could be easily referenced. The success of biobank establishment in PD/AD research allows detailed human genetic analyses in addition to comparison with valuable brain scans from Molecular Imaging Center (the PET, SPECT, fMRI and CT scan), Genomic Center, Proteomic Center and Metabolomic platform to construct a comprehensive patient database. Other than –omics detection, the sensitive SPR technique developed by Dr. Chien Chou, faculty of Graduate Institute of Electro-optical engineering, would allow a-synuclein and b-amyloid detection in trace amount hence could facilitate the disease early diagnosis.

(2) Cell and animal model establishment: In Parkinsonism study, research team has been successively produced pathogenic PINK1 and LARK2 Tg or KO mice and will continue to (A) investigate different PD candidate genes and explore how these gene products would lead to protein aggregation, behavioral abnormality and dopamine dysfunction; (B) uncover the underlying cellular mechanism of L-dopa-induced dyskinesia (LID) using 6-OHDA neurotoxin treated semi-PD mice as model and (C) examine how b-amyloid would interact with muscarinic receptor and HO-2 signaling to disrupt the circadian rhythm, an early symptom of AD; and (D) inspect how the pro-inflammatory mediators (such as bradykinin, IL-1b) and NADPH oxidase activation would lead to neuron/glia dysfunction and its involvement in metalloprotenase over-expression and MAPK/NF-kB signaling.  

       

(3) Domestic and international collaboration: One important goal served in the Neurodegenerative research team is to advance and expand our current research capability in order to collaborate with domestic and international research teams. Currently, NRC of CGMH has long-term collaboration with Erasmus medical center at Rotterdam, Netherlands for identifying the genetic variants from domestic familial PD patients. In addition, molecular imaging team participates extensively with numerous research centers and clinical sectors for international cohort study. Based on established platforms in HARC and disease animal models in Division of Neurodegenerative diseases, we expect to expand our research capacity in the future, increase international collaborations and become an international recognized AD/PD research center.

Overall, the established human genetic database and brain imaging profile in NRC, CGMH and disease animal and cell models in HARC would serve as valuable platforms that will benefit not only the research advance in neurodegenerative diseases, but could extensively apply to other neurological or psychiatric disorders (such as Schizophrenia and Major depression). The setup of these platforms, along with others in CGU, will be foreseeable to benefit in both research and teaching (both clinic and basic) and intensify the in-depth of our neuroscience study in Chang-Gung medical research.

 

Accomplishments

Huang HM, Hsiao IT (2016). Accelerating an Ordered-Subset Low-Dose X-Ray Cone Beam Computed Tomography Image Reconstruction with a Power Factor and Total Variation Minimization. PLoS One 11(4): e0153421.

Lin KJ, Hsiao IT, Hsu JL, Huang CC, Huang KL, Hsieh CJ, et al (2016). Imaging characteristic of dual-phase (18)F-florbetapir (AV-45/Amyvid) PET for the concomitant detection of perfusion deficits and beta-amyloid deposition in Alzheimer's disease and mild cognitive impairment. Eur J Nucl Med Mol Imaging 43(7): 1304-1314.

Lin YT, Kao SC, Day YJ, Chang CC, Chen JC (2016). Altered nociception and morphine tolerance in neuropeptide FF receptor type 2 over-expressing mice. European journal of pain 20(6): 895-906.

Lin YT, Liu TY, Yang CY, Yu YL, Chen TC, Day YJ, Chang CC, Huang GJ, Chen JC (2016). Chronic activation of NPFFR2 stimulates the stress-related depressive behaviors through HPA axis modulation. Psychoneuroendocrinology DOI: 10.1016/j.psyneuen.2016.05.014

Wu KY, Liu CY, Chen CS, Chen CH, Hsiao IT, Hsieh CJ, et al (2016). Beta-amyloid deposition and cognitive function in patients with major depressive disorder with different subtypes of mild cognitive impairment: (18)F-florbetapir (AV-45/Amyvid) PET study. Eur J Nucl Med Mol Imaging 43(6): 1067-1076.

Yang CM, Lin CC, Hsieh HL (2016). High-Glucose-Derived Oxidative Stress-Dependent Heme Oxygenase-1 Expression from Astrocytes Contributes to the Neuronal Apoptosis. Mol Neurobiol.

Chang CC, Hsiao IT, Huang SH, Lui CC, Yen TC, Chang WN, et al (2015). (1)(8)F-FP-(+)-DTBZ positron emission tomography detection of monoaminergic deficient network in patients with carbon monoxide related parkinsonism. Eur J Neurol 22(5): 845-852, e859-860.

Chang YF, Tsao KC, Liu YC, Chen YC, Yu PC, Huang YC, et al (2015). Diagnosis of human metapneumovirus in patients hospitalized with acute lower respiratory tract infection using a metal-enhanced fluorescence technique. J Virol Methods 213: 151-156.

Chen HT, Chen JC (2015). Role of the ventral tegmental area in methamphetamine extinction: AMPA receptor-mediated neuroplasticity. Learn Mem 22(3): 149-158.

Cheng ML, Wang CH, Shiao MS, Liu MH, Huang YY, Huang CY, et al (2015). Metabolic disturbances identified in plasma are associated with outcomes in patients with heart failure: diagnostic and prognostic value of metabolomics. J Am Coll Cardiol 65(15): 1509-1520.

Chiu CC, Yeh TH, Lai SC, Wu-Chou YH, Chen CH, Mochly-Rosen D, et al (2015). Neuroprotective effects of aldehyde dehydrogenase 2 activation in rotenone-induced cellular and animal models of parkinsonism. Experimental Neurology 263: 244-253.

Chou AH, Chen YL, Chiu CC, Yuan SJ, Weng YH, Yeh TH, et al (2015). T1-11 and JMF1907 ameliorate polyglutamine-expanded ataxin-3-induced neurodegeneration, transcriptional dysregulation and ataxic symptom in the SCA3 transgenic mouse. Neuropharmacology 99: 308-317.

Lan MY, Yeh TH, Chang YY, Kuo HC, Sun HS, Lai SC, et al (2015). Clinical and genetic analysis of Taiwanese patients with hereditary spastic paraplegia type 5. Eur J Neurol 22(1): 211-214.

Lin CC, Hsieh HL, Liu SW, Tseng HC, Hsiao LD, Yang CM (2015). BK Induces cPLA2 Expression via an Autocrine Loop Involving COX-2-Derived PGE2 in Rat Brain Astrocytes. Mol Neurobiol 51(3): 1103-1115.

Shih RH, Wang CY, Yang CM (2015). NF-kappaB Signaling Pathways in Neurological Inflammation: A Mini Review. Front Mol Neurosci 8: 77.

Tang HY, Ho HY, Wu PR, Chen SH, Kuypers FA, Cheng ML, et al (2015). Inability to maintain GSH pool in G6PD-deficient red cells causes futile AMPK activation and irreversible metabolic disturbance. Antioxid Redox Signal 22(9): 744-759.

Wang CH, Cheng ML, Liu MH, Shiao MS, Hsu KH, Huang YY, et al (2015). Increased p-cresyl sulfate level is independently associated with poor outcomes in patients with heart failure. Heart Vessels.

Yang CC, Lin CC, Chien PT, Hsiao LD, Yang CM (2015). Thrombin/Matrix Metalloproteinase-9-Dependent SK-N-SH Cell Migration is Mediated Through a PLC/PKC/MAPKs/NF-kappaB Cascade. Mol Neurobiol.

Yang CM, Hsieh HL, Yu PH, Lin CC, Liu SW (2015). IL-1beta Induces MMP-9-Dependent Brain Astrocytic Migration via Transactivation of PDGF Receptor/NADPH Oxidase 2-Derived Reactive Oxygen Species Signals. Mol Neurobiol 52(1): 303-317.

Yang HC, Cheng ML, Hua YS, Wu YH, Lin HR, Liu HY, et al (2015). Glucose 6-phosphate dehydrogenase knockdown enhances IL-8 expression in HepG2 cells via oxidative stress and NF-kappaB signaling pathway. J Inflamm (Lond) 12: 34.

Yang ST, Hsiao IT, Hsieh CJ, Chiang YH, Yen TC, Chiu WT, et al (2015). Accumulation of amyloid in cognitive impairment after mild traumatic brain injury. J Neurol Sci 349(1-2): 99-104.

Chang YF, Chao CH, Lin LY, Tsai CH, Chou C, Lee YJ (2014). Determination of urine cofilin-1 level in acute kidney injury using a high-throughput localized surface plasmon-coupled fluorescence biosensor. J Biomed Opt 19(1): 011004.

Chou AH, Chen YL, Hu SH, Chang YM, Wang HL (2014). Polyglutamine-expanded ataxin-3 impairs long-term depression in Purkinje neurons of SCA3 transgenic mouse by inhibiting HAT and impairing histone acetylation. Brain research 1583: 220-229.

Chou JS, Chen CY, Chen YL, Weng YH, Yeh TH, Lu CS, et al (2014). (G2019S) LRRK2 causes early-phase dysfunction of SNpc dopaminergic neurons and impairment of corticostriatal long-term depression in the PD transgenic mouse. Neurobiol Dis 68: 190-199.

Hsiao IT, Weng YH, Hsieh CJ, Lin WY, Wey SP, Kung MP, et al (2014). Correlation of Parkinson disease severity and 18F-DTBZ positron emission tomography. JAMA Neurol 71(6): 758-766.

Hsiao IT, Weng YH, Lin WY, Hsieh CJ, Wey SP, Yen TC, et al (2014). Comparison of 99mTc-TRODAT-1 SPECT and 18 F-AV-133 PET imaging in healthy controls and Parkinson's disease patients. Nucl Med Biol 41(4): 322-329.

Hsieh HL, Chi PL, Lin CC, Yang CC, Yang CM (2014). Up-regulation of ROS-dependent matrix metalloproteinase-9 from high-glucose-challenged astrocytes contributes to the neuronal apoptosis. Mol Neurobiol 50(2): 520-533.

Huang CY, Chen YL, Li AH, Lu JC, Wang HL (2014). Minocycline, a microglial inhibitor, blocks spinal CCL2-induced heat hyperalgesia and augmentation of glutamatergic transmission in substantia gelatinosa neurons. J Neuroinflammation 11: 7.

Lan MY, Chang YY, Yeh TH, Lai SC, Liou CW, Kuo HC, et al (2014). High frequency of SPG4 in Taiwanese families with autosomal dominant hereditary spastic paraplegia. BMC Neurol 14: 216.

Lin CC, Hsieh HL, Chi PL, Yang CC, Hsiao LD, Yang CM (2014). Upregulation of COX-2/PGE2 by ET-1 mediated through Ca2+-dependent signals in mouse brain microvascular endothelial cells. Mol Neurobiol 49(3): 1256-1269.

Lin CC, Lee IT, Chi PL, Hsieh HL, Cheng SE, Hsiao LD, et al (2014). C-Src/Jak2/PDGFR/PKCdelta-dependent MMP-9 induction is required for thrombin-stimulated rat brain astrocytes migration. Mol Neurobiol 49(2): 658-672.

Su LC, Tian YC, Chang YF, Chou C, Lai CS (2014). Rapid detection of urinary polyomavirus BK by heterodyne-based surface plasmon resonance biosensor. J Biomed Opt 19(1): 011013.

Hsieh HL, Lin CC, Hsiao LD, Yang CM (2013). High glucose induces reactive oxygen species-dependent matrix metalloproteinase-9 expression and cell migration in brain astrocytes. Mol Neurobiol 48(3): 601-614.

Lao CL, Lu CS, Chen JC (2013). Dopamine D3 receptor activation promotes neural stem/progenitor cell proliferation through AKT and ERK1/2 pathways and expands type-B and -C cells in adult subventricular zone. Glia 61(4): 475-489.

Lin CC, Hsieh HL, Shih RH, Chi PL, Cheng SE, Yang CM (2013). Up-regulation of COX-2/PGE2 by endothelin-1 via MAPK-dependent NF-kappaB pathway in mouse brain microvascular endothelial cells. Cell Commun Signal 11(1): 8.

Lin CC, Lee IT, Wu WB, Liu CJ, Hsieh HL, Hsiao LD, et al (2013). Thrombin mediates migration of rat brain astrocytes via PLC, Ca(2)(+), CaMKII, PKCalpha, and AP-1-dependent matrix metalloproteinase-9 expression. Mol Neurobiol 48(3): 616-630.

Meir YJ, Lin A, Huang MF, Lin JR, Weirauch MT, Chou HC, et al (2013). A versatile, highly efficient, and potentially safer piggyBac transposon system for mammalian genome manipulations. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27(11): 4429-4443.

Tseng HC, Lee IT, Lin CC, Chi PL, Cheng SE, Shih RH, et al (2013). IL-1beta promotes corneal epithelial cell migration by increasing MMP-9 expression through NF-kappaB- and AP-1-dependent pathways. PLoS One 8(3): e57955.

Wei KC, Chu PC, Wang HY, Huang CY, Chen PY, Tsai HC, et al (2013). Focused ultrasound-induced blood-brain barrier opening to enhance temozolomide delivery for glioblastoma treatment: a preclinical study. PLoS One 8(3): e58995.

Wei KC, Tsai HC, Lu YJ, Yang HW, Hua MY, Wu MF, et al (2013). Neuronavigation-guided focused ultrasound-induced blood-brain barrier opening: a preliminary study in swine. AJNR Am J Neuroradiol 34(1): 115-120.

Wu TC, Chen HT, Chang HY, Yang CY, Hsiao MC, Cheng ML, et al (2013). Mineralocorticoid receptor antagonist spironolactone prevents chronic corticosterone induced depression-like behavior. Psychoneuroendocrinology 38(6): 871-883.

Yang CM, Hsieh HL, Lin CC, Shih RH, Chi PL, Cheng SE, et al (2013). Multiple factors from bradykinin-challenged astrocytes contribute to the neuronal apoptosis: involvement of astroglial ROS, MMP-9, and HO-1/CO system. Mol Neurobiol 47(3): 1020-1033.

Yeh TH, Lai SC, Weng YH, Kuo HC, Wu-Chou YH, Huang CL, et al (2013). Screening for C9orf72 repeat expansions in parkinsonian syndromes. Neurobiol Aging 34(4): 1311 e1313-131

Chao CH, Chang YF, Chen HC, Lin LY, Yu PC, Chang YS, et al (2012). Detection of urine cofilin-1 from patients hospitalized in the intensive care unit using the metal-enhanced fluorescence technique. Sensor Actuat B-Chem 173: 184-190.

Chao KT, Tsao HH, Weng YH, Hsiao IT, Hsieh CJ, Wey SP, et al (2012). Quantitative analysis of binding sites for 9-fluoropropyl-(+)-dihydrotetrabenazine ([(1)(8)F]AV-133) in a MPTP-lesioned PD mouse model. Synapse 66(9): 823-831.

Chen CY, Weng YH, Chien KY, Lin KJ, Yeh TH, Cheng YP, et al (2012). (G2019S) LRRK2 activates MKK4-JNK pathway and causes degeneration of SN dopaminergic neurons in a transgenic mouse model of PD. Cell death and differentiation 19(10): 1623-1633.

Chen HT, Ruan NY, Chen JC, Lin TY (2012). Dopamine D2 receptor-mediated Akt/PKB signalling: initiation by the D2S receptor and role in quinpirole-induced behavioural activation. ASN Neuro 4(6): 371-382.

Chi PL, Chen YW, Hsiao LD, Chen YL, Yang CM (2012). Heme oxygenase 1 attenuates interleukin-1beta-induced cytosolic phospholipase A2 expression via a decrease in NADPH oxidase/reactive oxygen species/activator protein 1 activation in rheumatoid arthritis synovial fibroblasts. Arthritis and rheumatism 64(7): 2114-2125.

Hsiao IT, Huang CC, Hsieh CJ, Hsu WC, Wey SP, Yen TC, et al (2012). Correlation of early-phase 18F-florbetapir (AV-45/Amyvid) PET images to FDG images: preliminary studies. Eur J Nucl Med Mol Imaging 39(4): 613-620.

Hsieh HL, Lin CC, Chan HJ, Yang CM (2012a). c-Src-dependent EGF receptor transactivation contributes to ET-1-induced COX-2 expression in brain microvascular endothelial cells. J Neuroinflammation 9: 152.

Hsieh HL, Lin CC, Shih RH, Hsiao LD, Yang CM (2012). NADPH oxidase-mediated redox signal contributes to lipoteichoic acid-induced MMP-9 upregulation in brain astrocytes. J Neuroinflammation 9: 110.

Huang KL, Lin KJ, Ho MY, Chang YJ, Chang CH, Wey SP, et al (2012). Amyloid deposition after cerebral hypoperfusion: evidenced on [(18)F]AV-45 positron emission tomography. J Neurol Sci 319(1-2): 124-129.

Kung MP, Weng CC, Lin KJ, Hsiao IT, Yen TC, Wey SP (2012). Amyloid plaque imaging from IMPY/SPECT to AV-45/PET. Chang Gung Med J 35(3): 211-218.

Lin CC, Hsieh HL, Shih RH, Chi PL, Cheng SE, Chen JC, et al (2012). NADPH oxidase 2-derived reactive oxygen species signal contributes to bradykinin-induced matrix metalloproteinase-9 expression and cell migration in brain astrocytes. Cell Commun Signal 10(1): 35.

Liu HL, Yang HW, Hua MY, Wei KC (2012). Enhanced therapeutic agent delivery through magnetic resonance imaging-monitored focused ultrasound blood-brain barrier disruption for brain tumor treatment: an overview of the current preclinical status. Neurosurg Focus 32(1): E4.

Lu CS, Lai SC, Wu RM, Weng YH, Huang CL, Chen RS, et al (2012). PLA2G6 mutations in PARK14-linked young-onset parkinsonism and sporadic Parkinson's disease. Am J Med Genet B Neuropsychiatr Genet 159B(2): 183-191.

Ting CY, Fan CH, Liu HL, Huang CY, Hsieh HY, Yen TC, et al (2012). Concurrent blood-brain barrier opening and local drug delivery using drug-carrying microbubbles and focused ultrasound for brain glioma treatment. Biomaterials 33(2): 704-712.

Yang CM, Lin CC, Lee IT, Lin YH, Chen WJ, Jou MJ, et al (2012). Japanese encephalitis virus induces matrix metalloproteinase-9 expression via a ROS/c-Src/PDGFR/PI3K/Akt/MAPKs-dependent AP-1 pathway in rat brain astrocytes. J Neuroinflammation 9: 12.

Yang HW, Hua MY, Liu HL, Tsai RY, Chuang CK, Chu PC, et al (2012). Cooperative dual-activity targeted nanomedicine for specific and effective prostate cancer therapy. ACS Nano 6(2): 1795-1805.

Yang HW, Hua MY, Liu HL, Tsai RY, Pang ST, Hsu PH, et al (2012). An epirubicin-conjugated nanocarrier with MRI function to overcome lethal multidrug-resistant bladder cancer. Biomaterials 33(15): 3919-3930.

Chou AH, Chen SY, Yeh TH, Weng YH, Wang HL (2011). HDAC inhibitor sodium butyrate reverses transcriptional downregulation and ameliorates ataxic symptoms in a transgenic mouse model of SCA3. Neurobiol Dis 41(2): 481-488.

Chou AH, Lin AC, Hong KY, Hu SH, Chen YL, Chen JY, et al (2011). p53 activation mediates polyglutamine-expanded ataxin-3 upregulation of Bax expression in cerebellar and pontine nuclei neurons. Neurochem Int 58(2): 145-152.

Hua MY, Yang HW, Liu HL, Tsai RY, Pang ST, Chuang KL, et al (2011). Superhigh-magnetization nanocarrier as a doxorubicin delivery platform for magnetic targeting therapy. Biomaterials 32(34): 8999-9010.

Huang CL, Wu-Chou YH, Lai SC, Chang HC, Yeh TH, Weng YH, et al (2011). Contribution of glucocerebrosidase mutation in a large cohort of sporadic Parkinson's disease in Taiwan. Eur J Neurol 18(10): 1227-1232.

Lin YT, Ro LS, Wang HL, Chen JC (2011). Up-regulation of dorsal root ganglia BDNF and trkB receptor in inflammatory pain: an in vivo and in vitro study. J Neuroinflammation 8: 126.

Liu HL, Chen PY, Yang HW, Wu JS, Tseng IC, Ma YJ, et al (2011). In vivo MR quantification of superparamagnetic iron oxide nanoparticle leakage during low-frequency-ultrasound-induced blood-brain barrier opening in swine. J Magn Reson Imaging 34(6): 1313-1324.

Shih RH, Cheng SE, Hsiao LD, Kou YR, Yang CM (2011). Cigarette smoke extract upregulates heme oxygenase-1 via PKC/NADPH oxidase/ROS/PDGFR/PI3K/Akt pathway in mouse brain endothelial cells. J Neuroinflammation 8: 104.

Tung WH, Hsieh HL, Lee IT, Yang CM (2011). Enterovirus 71 induces integrin beta1/EGFR-Rac1-dependent oxidative stress in SK-N-SH cells: role of HO-1/CO in viral replication. Journal of cellular physiology 226(12): 3316-3329.

Wang HL, Chou AH, Wu AS, Chen SY, Weng YH, Kao YC, et al (2011). PARK6 PINK1 mutants are defective in maintaining mitochondrial membrane potential and inhibiting ROS formation of substantia nigra dopaminergic neurons. Biochimica et biophysica acta 1812(6): 674-684.

Yang HW, Hua MY, Liu HL, Huang CY, Tsai RY, Lu YJ, et al (2011). Self-protecting core-shell magnetic nanoparticles for targeted, traceable, long half-life delivery of BCNU to gliomas. Biomaterials 32(27): 6523-6532.

 

 

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