Elevated Levels of Naturally-Occurring Autoantibodies Against the Extracellular Domain of p75NTR Aggravate the Pathology of Alzheimer’s Disease

He, Chenyang; Tian, Ding-Yuan; Chen, Sihan; Jin, Wang-Sheng; Cheng, Yuan; Xin, Jia-Yan; Li, Weiwei; Zeng, Guihua; Tan, Cheng‐Rong; Jian, Jie-Ming; Fan, Dong-Yu; Ren, Jun-Rong; Liu, Yuhui; Wang, Yanjiang; Zeng, Fan

doi:10.1007/s12264-022-00936-4

Cited by 2 publications

(8 citation statements)

References 33 publications

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“…From the results of this study emerged a significant association between the rs2072446 variant and the risk of fAD. Since the polymorphism is located near the genetic region that codes for the cleavage region recognized by ADAM17, its variability may affect the cleavage efficiency of NGFR/p75 NTR and thus the release of NGFR/p75 NTR ECD [73]. However, this association did not remain significant after correction for multiple comparisons.…”

Section: Ngfr/p75 Ntr Genetic Variants and Admentioning

confidence: 97%

“…This effect is probable due to the fact that the NGFR/p75 NTR ECD contains the binding sites for Aβ − i.e., CRD1 and CRD2 domains − and for other ligands that can induce apoptosis through the activation of these receptors [72]. Thus, the impaired NGFR/p75 NTR ECD shedding and the imbalanced levels of NGFR/p75 NTR and NGFR/p75 NTR ECD could play an important role in regulating the production and clearance of Aβ [73]. Moreover, the PSEN1 M146V mutation increases γ-secretase cutting of NGFR/p75 NTR in vitro and potentially exacerbates the pathogenic outcomes observed in fAD [74].…”

Section: Expression and Signaling Pathways Of Ngfr/p75 Ntr In Admentioning

confidence: 99%

“…Moreover, the PSEN1 M146V mutation increases γ-secretase cutting of NGFR/p75 NTR in vitro and potentially exacerbates the pathogenic outcomes observed in fAD [74]. He and colleagues also reported an overproduction of naturally occurring autoantibodies against NGFR/p75 NTR ECD in AD patients, strengthening the role of the immune system and immunosenescence in the AD pathogenesis [73]. Further evidence about the involvement of NGFR/p75 NTR in AD derives from inactivation and ablation studies.…”

Section: Expression and Signaling Pathways Of Ngfr/p75 Ntr In Admentioning

confidence: 99%

“…In addition, the combination of CSF Aβ1-42, CSF Aβ42-40, CSF ptau181 or CSF ptau181/Aβ1-42 with CSF NGFR/p75 NTR ECD improves the diagnostic accuracy. More recently, He and colleagues [73] investigated the presence and alterations of naturally occurring autoantibodies against NGFR/p75 NTR ECD in AD patients, as well as their effects on AD pathology. From the results of this study emerged an increased levels of these naturally occurring antibodies in the CFS and a negative association between these and the CFS levels of NGFR/p75 NTR ECD in AD patients.…”

Section: Ngfr/p75 Ntr As a Biomarker Of Admentioning

confidence: 99%

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The Nerve Growth Factor Receptor (NGFR/P75<sup>ntr</sup>): A Major Player in Alzheimer’s Disease

Bruno¹,

Abondio²,

Montesanto³

et al. 2023

Preprint

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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., pro-NGF, 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. Besides 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.

show abstract

Section: Ngfr/p75 Ntr Genetic Variants and Admentioning

confidence: 97%

Section: Expression and Signaling Pathways Of Ngfr/p75 Ntr In Admentioning

confidence: 99%

Section: Expression and Signaling Pathways Of Ngfr/p75 Ntr In Admentioning

confidence: 99%

Section: Ngfr/p75 Ntr As a Biomarker Of Admentioning

confidence: 99%

See 2 more Smart Citations

The Nerve Growth Factor Receptor (NGFR/P75<sup>ntr</sup>): A Major Player in Alzheimer’s Disease

Bruno¹,

Abondio²,

Montesanto³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…This effect is probable due to the fact that the NGFR/p75 NTR ECD contains the binding sites for Aβ—i.e., CRD1 and CRD2 domains—and for other ligands that can induce apoptosis through the activation of these receptors [ 78 ]. Thus, the impaired NGFR/p75 NTR ECD shedding and the imbalanced levels of NGFR/p75 NTR and NGFR/p75 NTR ECD could play an important role in regulating the production and clearance of Aβ [ 79 ]. Moreover, the PSEN1 M146V mutation increases γ-secretase cutting of NGFR/p75 NTR in vitro and potentially exacerbates the pathogenic outcomes observed in fAD [ 80 ].…”

Section: Expression and Signaling Pathways Of Ngfr/p75 Ntr ...mentioning

confidence: 99%

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

Bruno

Abondio

Montesanto

et al. 2023

IJMS

View full text Add to dashboard Cite

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.

show abstract

Elevated Levels of Naturally-Occurring Autoantibodies Against the Extracellular Domain of p75NTR Aggravate the Pathology of Alzheimer’s Disease

Cited by 2 publications

References 33 publications

The Nerve Growth Factor Receptor (NGFR/P75<sup>ntr</sup>): A Major Player in Alzheimer’s Disease

The Nerve Growth Factor Receptor (NGFR/P75<sup>ntr</sup>): A Major Player in Alzheimer’s Disease

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

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