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).
Highlights
Transthyretin (TTR), a carrier protein for thyroxine and retinol present in the plasma and cerebrospinal fluid (CSF), has been shown to sequester the amyloid beta-peptide deposition in the brain [1] [2]
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)
It has been suggested that uni-directional secretion of TTR proteins to the CSF plays a key role in the transfer of thyroxine (T4) from the blood to the CSF, as TTR may drive thyroxin hormones (TH) across the blood-CSF barrier [6]
Summary
Transthyretin (TTR), a carrier protein for thyroxine and retinol present in the plasma and cerebrospinal fluid (CSF), has been shown to sequester the amyloid beta-peptide deposition in the brain [1] [2]. TTR protein has the ability to enhance neurite outgrowth in vitro, plays apivotal role in nerve regeneration process and provides neuroprotection in the peri-. TTR binds several different proteins including megalin (LRP-2), RAGE (receptor for advanced glycation end products) and IGF-IR (insulin-like growth factor 1 receptor) [30] [31] [32] [33] [34] to activate the downstream signaling pathways. The second pathway through which TTR stimulation rescues cell death and neurite loss is by activating Bcl protein family members in megalin-dependent manners. TTR triggered by its interaction with a well-known neuroprotective megalin-dependent signaling pathways promotes a robust neurite outgrowth response in hippocampal neurons by the upregulation of intracellular calcium and MAPK pathways (Figure 1). Keeping in view the above discussions, TTR might be regarded as a neurotrophic factor, both in neurite outgrowth and neuroprotection under physiological conditions
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