Research Overview Microarray Gene and miRNA Expression Studies: Looking for New Therapeutic Targets for Frontotemporal Lobar Degeneration Elena Milanesi 1 * and Andrea Pilotto 2,3 1 Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel 2 Department of Neurodegeneration, University of Tübingen, Tübingen, 72074, Germany 3 Centre for Ageing Brain and Neurodegenerative Disorders, University of Brescia, Brescia, 25123, Italy Strategy, Management and Health Policy Enabling Technology, Genomics, Proteomics Preclinical Research Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics Clinical Development Phases I-III Regulatory, Quality, Manufacturing Postmarketing Phase IV ABSTRACT Frontotemporal lobar degeneration (FTLD) encompasses a spectrum of neurodegenerative disorders characterized by behavioral, executive and language impairment, with a common overlap with parkinsonism and motor-neuron disease. Despite an increased understanding of its genetic background and molecular pathophysiology, FTLD is still an orphan disorder and there are currently no effective therapies available. In this brief overview we report the results obtained by several high-throughput and bioinformatic studies aimed at discovering impairment in the transcriptional profiles in brain and periph- eral tissues from FTLD patients and in animal models. Taken together, all these results provide an interesting but still fragmentary list of genes and miRNAs whose role in FTLD should be thoroughly investigated. Drug Dev Res 75 : 366–371, 2014. © 2014 Wiley Periodicals, Inc. Key words: frontotemporal degeneration; microarray; gene expression analyses; genetics; therapy; drug targets INTRODUCTION Genomics, proteomics and metabolomics have profoundly changed the traditional approaches to drug discovery and development. In many fields of medical science, such as in oncology, potential drug targets are increasingly being identified combining high- throughput sequencing, microarray gene expression, microRNA (miRNA) studies and recently next genera- tion sequencing (NGS) data [Koboldt et al., 2013]. Given its strong genetic background, frontotemporal lobar degeneration (FTLD) probably represents one of the best models for translational research in neurodegenerative disease. However, despite the large amount of genetic, proteomic, clinical and pathological data available, only few targets have so far been identi- fied and reached the evaluation in clinical setting [Miller et al., 2014]. In this brief overview we summa- rize published gene expression/miRNA studies con- ducted in preclinical FTLD models, on post-mortem human brain tissues and in vivo, with the aim to high- light the most promising discoveries in FTLD research, underlining the importance of bioinformatics as an ulti- mate strategy in translational research. FTLD OVERVIEW: CLINICAL, GENETICS AND NEUROPATHOLOGY Frontotemporal dementia (FTD) refers to a group of clinically heterogeneous disorders characterized by *Correspondence to: Elena Milanesi, Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel. E-mail: elena.k.milanesi@gmail.com Published online in Wiley Online Library (wileyonlinelibrary .com). DOI: 10.1002/ddr.21224 DRUG DEVELOPMENT RESEARCH 75 : 366–371 (2014) DDR © 2014 Wiley Periodicals, Inc.