Alzheimer's disease (AD) is a progressive mental illness characterized by memory loss and multiple cognitive impairments. In the last several decades, significant progress has been made in understanding basic biology, molecular mechanisms, and development of biomarkers and therapeutic drugs. Multiple cellular changes are implicated in the disease process including amyloid beta and phosphorylation of tau synaptic damage and mitochondrial dysfunction in AD. Among these, amyloid beta is considered a major player in the disease process. Recent advancements in molecular biology revealed that microRNAs (miRNAs) are considered potential biomarkers in AD with a focus on amyloid beta. In this article we discussed several aspects of AD including its prevalence, classifications, risk factors, and amyloid species and their accumulation in subcellular compartments. This article also discusses the discovery and biogenesis of miRNAs and their relevance to AD. Today's research continues to add to the wealth of miRNA data that has been accumulated, however, there still lacks clear-cut understanding of the physiological relevance of miRNAs to AD. MiRNAs appear to regulate translation of gene products in AD and other human diseases. However, the mechanism of how many of these miRNAs regulate both the 5 and 3 UTR of amyloid precursor protein (APP) processing is still being extrapolated. Hence, we still need more research on miRNAs and APP/amyloid beta formation in the progression and pathogenesis of AD.

Li-Fraumeni syndrome (LFS) is a rare hereditary cancer disorder with highly variable clinical outcomes that results from germline mutations in the TP53 gene. Here we report that the quaternary structure of p53 is an important factor affecting cellular functions and the clinical outcomes of LFS patients (n = 87). Specifically, carriers of monomeric p53 mutants (n = 56) exhibited complete penetrance, with a 2.11-fold greater risk of cancer-related death (95% confidence interval [CI] = 1.07 to 4.30) and a statistically significantly lower median survival age as compared with carriers of multimeric (dimeric or tetrameric, n = 31) p53 mutants (33 years, 95% CI = 30 to 50, vs 51 years, 95% CI = 40 to NA, respectively, two-sided P = .03), who presented incomplete penetrance. Cellular functional assays using p53-null H1299 cells expressing clinically relevant p53 mutants confirmed that the cellular effects observed upon loss of p53 oligomerization are associated with clinical outcomes of LFS patients. The association between p53 oligomeric state and clinical phenotype suggests that TP53 mutations are not all equivalent and supports the implementation of new genotype-adapted guidelines for the management of LFS patients with TP53 mutations in the oligomerization domain.

Epigenetic dysregulation of miR-34A may comprise an important path in TP53-associated cancer predisposition and represents a therapeutically actionable target with potential clinical relevance.

The objective of our study is to investigate the modulation of Type I Interferon induction of an antiviral state by Human Immunodeficiency Virus (HIV). Type I Interferons including IFN-α are key innate immune cytokines that activate the JAK/STAT pathway leading to the expression of ISGs (Interferon Stimulated Genes). ISGs consist of a pantheon of antiviral genes whose expression establishes the antiviral state that limits local viral infection in IFN-α stimulated microenvironments. Our previous studies have shown that HIV proteins disrupt the induction of Type I interferon (IFN-α) by degradation of IPS-1 (IFN-β promoter stimulator-1) which acts as an adaptor protein for the upregulation and release of IFN-α into local microenvironment via the RIG-I (retinoic acid-inducible gene 1)-Like Receptor (RLR) signaling pathway. However, IFN-α is still released from other sources such as plasmacytoid dendritic cells (pDCs) via Toll-like Receptor (TLR) dependent recognition of HIV. Here we report that the activation of the JAK/STAT pathway by IFN-α stimulation is disrupted by HIV proteins Vpu and Nef. Vpu and Nef both reduce IFN-α induction of STAT1 phosphorylation. This study shows that regardless of the presence of IFN-α in the local microenvironment, HIV would still be able to avoid antiviral protection induced by IFN-α signaling. These findings provide additional insight into how HIV acts to block multiple signaling points that would lead to the upregulation of ISGs. HIV is allowed to replicate more effectively if there is a reduction in ISG expressions induced by IFN-α.