The role of BACE1-AS and BC200 long non coding RNAs in Alzheimer’s disease

Introduction: Alzheimer’s disease (AD) is one of the most common neurodegenerative disease and accounts for >80% of dementia cases in people aged older than 65 years. Long noncoding RNAs (lncRNAs) comprise a subgroup of noncoding RNAs longer than 200 nucleotides, accounting for the largest proportion of the mammalian noncoding transcriptome. LncRNAs are implicated in the development of axonal and dendritic connections, and additionally, in synaptic modulation that is correlated with neural network plasticity and that may also participate in the generation of long-term potentiation that underlies learning and memory.Description: LncRNA BACE1-AS is highly expressed in AD patients and in amyloid precursor protein (APP) transgenic mice. This LncRNA is transcripted by the antisense strand of BACE1 (a protein coding gene) and plays the key role in increasing BACE1 mRNA stability by masking the binding site for miR-485-5p and preventing miRNA-induced translational repression of BACE1 mRNA. This mechanism leads to upregulating of BACE1 protein. BACE1 is a crucial enzyme that cleaves APP and generates amyloid β (Aβ) peptides, which form amyloid plaques on the neurons. In addition to BACE1-AS, the lncRNA BC1 (in mice) and BC200 (in humans) can control the expression of BACE1 mRNA. These lncRNAs modulate gene expression at translational level. BC200 levels is increased in brain regions that are preferentially affected in AD and exhibits abnormal subcellular localization. The primate BC200 is also associated with synapse plasticity.Discussion and conclusion: As dysregulation of lncRNAs involved in AD, these RNAs are desirable candidates as AD biomarkers and could help identify rational therapeutic strategies. An enhanced understanding of lncRNA biology could open more avenues to early AD diagnosis and treatment.