The Nerve Growth Factor Receptor (NGFR/p75NTR): A Major Player in Alzheimer’s Disease

Abstract

Alzheimer’s disease (AD) represents the most prevalent type of dementia in elderly people, primarily characterized by brain accumulation of beta-amyloid (Aβ) peptides, derived from Amyloid Precursor Protein (APP), in the extracellular space (amyloid plaques) and intracellular deposits of the hyperphosphorylated form of the protein tau (p-tau; tangles or neurofibrillary aggregates). The Nerve growth factor receptor (NGFR/p75NTR) represents a low-affinity receptor for all known mammalians neurotrophins (i.e., proNGF, NGF, BDNF, NT-3 e NT-4/5) and it is involved in pathways that determine both survival and death of neurons. Interestingly, also Aβ peptides can blind to NGFR/p75NTR making it the “ideal” candidate in mediating Aβ-induced neuropathology. In addition to pathogenesis and neuropathology, several data indicated that NGFR/p75NTR could play a key role in AD also from a genetic perspective. Other studies suggested that NGFR/p75NTR could represent a good diagnostic tool, as well as a promising therapeutic target for AD. Here, we comprehensively summarize and review the current experimental evidence on this topic.

Identification of candidate biomarkers and pathways associated with multiple sclerosis using bioinformatics and next generation sequencing data analysis

“…Alerted expression of MS4A2 [356], CD48 [357], HLA-DRB5 [358], FCGR2B [359], CCL5 [360], CCL3 [361], LTF (lactotransferrin) [362], GPNMB (glycoprotein nmb) [363], CTLA4 [364], TRIML2 [365], PTGDR (prostaglandin D2 receptor) [366], DRD3 [367], LHCGR (luteinizing hormone/choriogonadotropin receptor) [368], CD163 [369], PRPH (peripherin) [211], MSR1 [370], HGF (hepatocyte growth factor) [371], TTR (transthyretin) [372], IL9 [373], ADM (adrenomedullin) [374], CHI3L1 [375], CNP (2',3'-cyclic nucleotide 3' phosphodiesterase) [376], CDH1 [377], OLIG2 [378], KLK8 [379]. CFTR (CF transmembrane conductance regulator) [380], ABCA2 [381], HK2 [382], NGFR (nerve growth factor receptor) [383], TF (transferrin) [384], GLUL (glutamate-ammonia ligase) [324], ADAMTS4 [385], BIN1 [386], HSPA2 [387], LMNA (lamin A/C) [388], HSD11B1 [389], HTRA1 [390], APLP1 [391], MT3 [392], ADORA1 [393], DYSF (dysferlin) [394], SLC24A4 [395], RHOB (ras homolog family member B) [396], NINJ2 [397], LRP2…”

“…Alerted expression of MS4A2 [356], CD48 [357], HLA-DRB5 [358], FCGR2B [359], CCL5 [360], CCL3 [361], LTF (lactotransferrin) [362], GPNMB (glycoprotein nmb) [363], CTLA4 [364], TRIML2 [365], PTGDR (prostaglandin D2 receptor) [366], DRD3 [367], LHCGR (luteinizing hormone/choriogonadotropin receptor) [368], CD163 [369], PRPH (peripherin) [211], MSR1 [370], HGF (hepatocyte growth factor) [371], TTR (transthyretin) [372], IL9 [373], ADM (adrenomedullin) [374], CHI3L1 [375], CNP (2’,3’-cyclic nucleotide 3’ phosphodiesterase) [376], CDH1 [377], OLIG2 [378], KLK8 [379]. CFTR (CF transmembrane conductance regulator) [380], ABCA2 [381], HK2 [382], NGFR (nerve growth factor receptor) [383], TF (transferrin) [384], GLUL (glutamate-ammonia ligase) [324], ADAMTS4 [385], BIN1 [386], HSPA2 [387], LMNA (lamin A/C) [388], HSD11B1 [389], HTRA1 [390], APLP1 [391], MT3 [392], ADORA1 [393], DYSF (dysferlin) [394], SLC24A4 [395], RHOB (ras homolog family member B) [396], NINJ2 [397], LRP2 [398], LIPC (lipase C, hepatic type) [399], DHCR7 [400], SCD (stearoyl-CoA desaturase) [401], F11 [402], PFKL (phosphofructokinase, liver type) [403], ALDH1A1 [404], SPON1 [405] and CTNNA3 [406] are significantly associated with the Alzheimer’s Disease. CCR4 [407], CCR2 [408], CD48 [409], CD28 [410], CCL3 [411], CTLA4 [412], C6 [413], MICB (MHC class I polypeptide-related sequence B) [414], DRD3 [415], HGF (hepatocyte growth factor) [416], DIO3 [417], TTR (transthyretin) [418], GRHL3 [419], VEGFA (vascular endothelial growth factor A) [420], ADM (adrenomedull...…”

“…TAB2 [131], LMNA (lamin A/C) [330], HGF (hepatocyte growth factor) [494] and CCL5 [486] migt play an important role in the occurrence and development of obesity. CFTR (CF transmembrane conductance regulator) [380], RHOB (ras homolog family member B) [396], LMNA (lamin A/C) [388], HGF (hepatocyte growth factor) [371], CCL5 [360] and NGFR (nerve growth factor receptor) [383] were altered expression in the Alzheimer’s Disease. CFTR (CF transmembrane conductance regulator) [551], LMNA (lamin A/C) [558], ERBB3 [331], HGF (hepatocyte growth factor) [494], CCL5 [540] and NGFR (nerve growth factor receptor) [554] have been demonstrated to accelerate hypertension progression.…”

Genetically engineered neural stem cells (NSCs) therapy for neurological diseases; state‐of‐the‐art

“…Like BDNF gene therapy, NGF delivery using NSCs into okadaic acid‐induced AD rats increased learning and memory function 178 . Basal forebrain cholinergic neurons need NGF for maintenance of cholinergic phenotype, are important for cognition, and degenerate early in AD 179,180 . The proNGF maturation is compromised in preclinical and clinical AD while increasing the degradation of mature NGF degradation.…”

“…178 Basal forebrain cholinergic neurons need NGF for maintenance of cholinergic phenotype, are important for cognition, and degenerate early in AD. 179,180 The proNGF maturation is compromised in preclinical and clinical AD while increasing the degradation of mature NGF degradation. These alterations have an association with cognition, pathology, and cholinergic tone, and may regard as novel biomarkers and therapeutic targets.…”