TITLE:
Transthyretin—A Key Gene Involved in Regulating Learning and Memory in Brain, and Providing Neuroprotection in Alzheimer Disease via Neuronal Synthesis of Transthyretin Protein
AUTHORS:
Javed Iqbal
KEYWORDS:
Learning and Memory, TTR—Transthyretin, AD—Alzheimer Disease, CSF—Cerebrospinal Fluid, MAPK—Mitogen-Activated Protein Kinases, CREB—cAMP Response Element Binding Protein, ERK—Extracellular Receptor Kinases, Aβ—Amyloid Beta, LTP—Long-Term Potentiation, LTD—Long-Term Depression
JOURNAL NAME:
Journal of Behavioral and Brain Science,
Vol.8 No.2,
February
13,
2018
ABSTRACT: Transthyretin (TTR), a carrier protein present in the liver and choroid plexus of the brain, has been shown to be responsible for binding thyroid hormone thyroxin (T4) and retinol in plasma and cerebrospinal fluid (CSF). TTR aids in sequestering of beta-amyloid peptides Aβ deposition, and protects the brain from trauma, ischemic stroke and Alzheimer disease (AD). Accordingly, hippocampal gene expression of TTR plays a significant role in learning and memory as well as in simulation of spatial memory tasks. TTR via interacting with transcription factor CREB regulates this process and decreased expression leads to memory deficits. By different signaling pathways, like MAPK, AKT, and ERK via Src, TTR provides tropical support through megalin receptor by promoting neurite outgrowth and protecting the neurons from traumatic brain injury. TTR is also responsible for the transient rise in intracellular Ca2+ via NMDA receptor, playing a dominant role under excitotoxic conditions. In this review, we tried to shed light on how TTR is involved in maintaining normal cognitive processes, its role in learning and memory, under memory deficit conditions; by which mechanisms it promotes neurite outgrowth; and how it protects the brain from Alzheimer disease (AD).