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 β-
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 β-
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.