The controlling pathways and mechanisms of action of some endogenous miRNAs in animal models of neurodegenerative disorders are defined in the succeeding parts. This moreover generates a broad map to elucidate how these miRNAs are expressed in neurodegenerative disorders.
miR-9
According to Sempere et al. (2004), miR-9 is highly expressed in the brains of equally emerging and mature mammals. According to Tan et al. (2012), miR-9 is vital for the growing and differentiation of brain stem cells. In detail, inhibition of miR-9 outcomes in improved cell migratory ability and reduced proliferation of brain progenitor cells (Delaloy et al. 2010). Studies have revealed that diverse species have separate sets of miRNAs, and the differences in miR-9 may donate to the differences in the size, shape, and function of vertebrates’ brains. This could be as a result of the intimate relationship between miR-9 and brain stem cell development and proliferation (Alwin Prem Anand et al. 2020). By attaching with the 3′-UTR of Hes1 mRNA and regulating the levels of expression of Hes1 protein, miR-9 can disturb these processes. Hes1 protein is reduced in response to overexpression of miR-9, which causes neuronal differentiation and cell cycle termination (Tan et al. 2012). MiR-9’s chief function in neurogenesis is to decrease the expression of hairy1 mRNA. According to Bonev et al. (2011), the miR-9/hairy1 complex affects cell death through p53 and proliferation over cyclin D/p27. MiR-9 has a part in the neuronal cell cycle, which can effect neural growth and development. It also prevents the levels of expression Gsh2 and Foxg1 proteins, allowing Cajal-Retzius cells and preterm neurons to differentiate appropriately (Dajas-Bailador et al. 2012; Shibata et al. 2011).
The family miR-29
The miR-29 family is composed of miRNA groups that, among additional things, generate miR-29s, miR-29a, miR-29b, and miR-29c. They have the same goal subsequently they share lots of the same sequence (Kriegel et al. 2012). Loss of miR-29 marks in improved expression of T-bet and IFN. Transcription factors T-bet and IFN collaborate to control type 1 inflammatory responses. They are existing in many diverse cell types, such as lymphocytes and antigen-presenting cells. The immune system defends the body from a diversity of pathogenic bacteria, but autoimmune diseases can rise when the body’s resistances are not stable in terms of the timing and length of these immune components’ expression (Smith et al. 2012; Steiner et al. 2011). The immune reaction is strongly tense to the miR-29 family, which distracts Th1 development, B cell survival, and terminal differentiation through PI3K signal transduction (Hines et al. 2020). According to Rong et al. (2020), miR-29 displays a role in controling the Akt signaling pathway in rat models of cerebral infarction, which can prevent neuronal death. The hippocampus, cerebellar Purkinje cells, and olfactory bulb neurons are three regions where distinct participants of the miR-29 family are significantly expressed. Neurons in the hippocampal CA1 zone last to die gradually after transient forebrain ischaemia, which influences the progression of the disease. miR-29a triggers hippocampal neuronal cell death and resistances CA1 from lengthy neuronal death after forebrain ischaemia by targeting PUMA, a member of the pro-apoptotic Bcl2 family (Ouyang et al.2023).
MiR-15
As the miR-15/107 group was discovered, its role in humans has been investigated extensive. In vertebrate species, these miRNAs are involved to control the expression of genes involved in cell cycle and cell division, metabolism, the immune response, and apoptosis. The miR-15/107 family has been linked to neurological disorders, cardiovascular disease, and human cancer (Parsi et al. 2015; Finnerty et al. 2010; Liu and Wang 2012). The miR-15/107 family also controls CDK5R1/p35, which is vital for brain growth and function and has been associated to a number of neurological disorders, including AD. In fact, downregulation of the miR-15/107 family increases CDK5R1/p35 levels and, as a result, rises CDK5 action, which is involved in the etiology of AD (Moncini et al. 2017). Separately after its effects on the nervous system, miR-15 also has an effect on the immune system. It has been revealed that miR-15 can aid pre-B cells transition from proliferation to differentiation (Lindner et al. 2017); restrict the T cell cycle, existence, and memory T cell differentiation (Gagnon et al. 2019); and regulate the maturing of natural killer cells by opposite Myb (Sullivan et al. 2015). The immune system is controlled in the body when miR-15 regulates these immune cells. It can also regulate cell division and apoptosis. miR-15 and miR-16 have been recognized as direct transcription targets of E2F1. Targeting cyclin E inhibits e2F-promoted proliferation (Ofir et al. 2011).