PMID- 28956815 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20191120 IS - 2073-4425 (Print) IS - 2073-4425 (Electronic) IS - 2073-4425 (Linking) VI - 8 IP - 10 DP - 2017 Sep 28 TI - BARHL1 Is Downregulated in Alzheimer's Disease and May Regulate Cognitive Functions through ESR1 and Multiple Pathways. LID - 10.3390/genes8100245 [doi] LID - 245 AB - The Transcription factor BarH like homeobox 1 (BARHL1) is overexpressed in medulloblastoma and plays a role in neurogenesis. However, much about the BARHL1 regulatory networks and their functions in neurodegenerative and neoplastic disorders is not yet known. In this study, using a tissue microarray (TMA), we report for the first time that BARHL1 is downregulated in hormone-negative breast cancers and Alzheimer's disease (AD). Furthermore, using an integrative bioinformatics approach and mining knockout mouse data, we show that: (i) BARHL1 and Estrogen Receptor 1 (ESR1) may constitute a network that regulates Neurotrophin 3 (NTF3)- and Brain Derived Neurotrophic Factor (BDNF)-mediated neurogenesis and neural survival; (ii) this is probably linked to AD pathways affecting aberrant post-translational modifications including SUMOylation and ubiquitination; (iii) the BARHL1-ESR1 network possibly regulates beta-amyloid metabolism and memory; and (iv) hsa-mir-18a, having common key targets in the BARHL1-ESR1 network and AD pathway, may modulate neuron death, reduce beta-amyloid processing and might also be involved in hearing and cognitive decline associated with AD. We have also hypothesized why estrogen replacement therapy improves AD condition. In addition, we have provided a feasible new mechanism to explain the abnormal function of mossy fibers and cerebellar granule cells related to memory and cognitive decline in AD apart from the Tau and amyloid pathogenesis through our BARHL1-ESR1 axis. FAU - Barh, Debmalya AU - Barh D AD - Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal 721172, India. dr.barh@gmail.com. AD - Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil. dr.barh@gmail.com. FAU - Garcia-Solano, Maria E AU - Garcia-Solano ME AD - Department of Pathology, Santa Lucia General University Hospital (HGUSL), C/Mezquita s/n, 30202 Cartagena, Spain. garciasolano2002@yahoo.com. AD - Catholic University of Murcia (UCAM), 30107 Murcia, Spain. garciasolano2002@yahoo.com. FAU - Tiwari, Sandeep AU - Tiwari S AD - Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal 721172, India. sandip_sbtbi@yahoo.com. AD - Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil. sandip_sbtbi@yahoo.com. FAU - Bhattacharya, Antaripa AU - Bhattacharya A AD - Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal 721172, India. antaripa1210@gmail.com. FAU - Jain, Neha AU - Jain N AD - Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal 721172, India. mymailtoneha@gmail.com. FAU - Torres-Moreno, Daniel AU - Torres-Moreno D AD - Department of Pathology, Santa Lucia General University Hospital (HGUSL), C/Mezquita s/n, 30202 Cartagena, Spain. daniel-torres@orange.es. AD - Catholic University of Murcia (UCAM), 30107 Murcia, Spain. daniel-torres@orange.es. FAU - Ferri, Belen AU - Ferri B AD - Department of Pathology, Virgen Arrixaca University Hospital (HUVA), Ctra. Madrid Cartagena sn, 30120 El Palmar, Spain. belen.ferri@carm.es. FAU - Silva, Artur AU - Silva A AD - Instituto de Ciencias Biologicas, Universidade Federal do Para, Rua Augusto Correa, 01-Guama, Belem, PA 66075-110, Brazil. arturluizdasilva@gmail.com. FAU - Azevedo, Vasco AU - Azevedo V AD - Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG 31270-901, Brazil. vascoariston@gmail.com. FAU - Ghosh, Preetam AU - Ghosh P AD - Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal 721172, India. pghosh@vcu.edu. AD - Department of Computer Science, Virginia Commonwealth University, Richmond, VA 23284, USA. pghosh@vcu.edu. FAU - Blum, Kenneth AU - Blum K AD - Department of Psychiatry & McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL 32610, USA. drd2gene@gmail.com. FAU - Conesa-Zamora, Pablo AU - Conesa-Zamora P AD - Department of Pathology, Santa Lucia General University Hospital (HGUSL), C/Mezquita s/n, 30202 Cartagena, Spain. pablo.conesa@carm.es. AD - Catholic University of Murcia (UCAM), 30107 Murcia, Spain. pablo.conesa@carm.es. FAU - Perry, George AU - Perry G AD - UTSA Neurosciences Institute and Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, USA. george.perry@case.edu. AD - Department of Pathology, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. george.perry@case.edu. LA - eng GR - G12 MD007591/MD/NIMHD NIH HHS/United States PT - Journal Article DEP - 20170928 PL - Switzerland TA - Genes (Basel) JT - Genes JID - 101551097 PMC - PMC5664095 OTO - NOTNLM OT - Alzheimer's disease OT - bioinformatics OT - estrogen OT - microRNA OT - signaling COIS- The authors declare no conflict of interest. EDAT- 2017/09/29 06:00 MHDA- 2017/09/29 06:01 PMCR- 2017/10/01 CRDT- 2017/09/29 06:00 PHST- 2017/08/07 00:00 [received] PHST- 2017/09/13 00:00 [revised] PHST- 2017/09/20 00:00 [accepted] PHST- 2017/09/29 06:00 [entrez] PHST- 2017/09/29 06:00 [pubmed] PHST- 2017/09/29 06:01 [medline] PHST- 2017/10/01 00:00 [pmc-release] AID - genes8100245 [pii] AID - genes-08-00245 [pii] AID - 10.3390/genes8100245 [doi] PST - epublish SO - Genes (Basel). 2017 Sep 28;8(10):245. doi: 10.3390/genes8100245.