The Role of RIN3 Gene in Alzheimer’s Disease Pathogenesis: a Comprehensive Review

• Published in: Molecular neurobiology Vol. 61; no. 6; pp. 3528 - 3544
• Main Authors: Meshref, Mostafa, Ghaith, Hazem S., Hammad, Mohamed Ahmed, Shalaby, Mahmoud Mohamed Mohamed, Ayasra, Faris, Monib, Fatma Ahmed, Attia, Mohamed S., Ebada, Mahmoud A., Elsayed, Hanaa, Shalash, Ali, Bahbah, Eshak I.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-06-2024; Springer Nature B.V
• Subjects: Age; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Animals; Biomedical and Life Sciences; Biomedicine; Blood-brain barrier; Brain - metabolism; Brain - pathology; Cell Biology; Dementia disorders; Genetic factors; Guanine nucleotide exchange factor; Guanine Nucleotide Exchange Factors - genetics; Guanine Nucleotide Exchange Factors - metabolism; Humans; Immunological memory; Neurobiology; Neurodegenerative diseases; Neurology; Neurosciences; Pathogenesis; Protein folding; Senile plaques; Tau protein; β-Amyloid; Ras and Rab Interactor 3; RIN3; Alzheimer’s disease; Dementia
• ISSN: 0893-7648; 1559-1182; 1559-1182
• DOI: 10.1007/s12035-023-03802-0

Alzheimer’s disease (AD) is a globally prevalent form of dementia that impacts diverse populations and is characterized by progressive neurodegeneration and impairments in executive memory. Although the exact mechanisms underlying AD pathogenesis remain unclear, it is commonly accepted that the aggregation of misfolded proteins, such as amyloid plaques and neurofibrillary tau tangles, plays a critical role. Additionally, AD is a multifactorial condition influenced by various genetic factors and can manifest as either early-onset AD (EOAD) or late-onset AD (LOAD), each associated with specific gene variants. One gene of particular interest in both EOAD and LOAD is RIN3, a guanine nucleotide exchange factor. This gene plays a multifaceted role in AD pathogenesis. Firstly, upregulation of RIN3 can result in endosomal enlargement and dysfunction, thereby facilitating the accumulation of beta-amyloid (Aβ) peptides in the brain. Secondly, RIN3 has been shown to impact the PICLAM pathway, affecting transcytosis across the blood-brain barrier. Lastly, RIN3 has implications for immune-mediated responses, notably through its influence on the PTK2B gene. This review aims to provide a concise overview of AD and delve into the role of the RIN3 gene in its pathogenesis.