ProNGF and Neurodegeneration in Alzheimer’s Disease

Fahnestock, Margaret; Shekari, Arman

doi:10.3389/fnins.2019.00129

Cited by 98 publications

(93 citation statements)

References 170 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Likewise, KLK6 can release enkephalin from pro-enkephalin precursors, similarly to the canonical processing performed by the enzyme furin (Silva et al, 2017). It has been proposed that alterations in the enzymatic pathway that controls the maturation of pro-nerve growth factor (NGF) to NGF and its subsequent degradation could be relevant in neurodegenerative processes such as Alzheimer's disease that affect the activity of basal cholinergic neurons of the forebrain (Fahnestock and Shekari, 2019;Mitra et al, 2019;Mufson et al, 2019). A role for KLK8 in the expression of NGF at the skin has been described, but studies directed to show whether that KLK8 or other KLKs influence the bioavailability of NGF in the CNS have not yet been explored (Shingaki et al, 2012).…”

Section: Klks As Signaling Moleculesmentioning

confidence: 99%

Involvement of Kallikrein-Related Peptidases in Nervous System Disorders

Mella

Figueroa

Otth

et al. 2020

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Kallikrein-related peptidases (KLKs) are a family of serine proteases that when dysregulated may contribute to neuroinflammation and neurodegeneration. In the present review article, we describe what is known about their physiological and pathological roles with an emphasis on KLK6 and KLK8, two KLKs that are highly expressed in the adult central nervous system (CNS). Altered expression and activity of KLK6 have been linked to brain physiology and the development of multiple sclerosis. On the other hand, altered levels of KLK6 in the brain and serum of people affected by Alzheimer's disease and Parkinson's disease have been documented, pointing out to its function in amyloid metabolism and development of synucleinopathies. People who have structural genetic variants of KLK8 can suffer mental illnesses such as intellectual and learning disabilities, seizures, and autism. Increased expression of KLK8 has also been implicated in schizophrenia, bipolar disorder, and depression. Also, we discuss the possible link that exists between KLKs activity and certain viral infections that can affect the nervous system. Although little is known about the exact mechanisms that mediate KLKs function and their participation in neuroinflammatory and neurodegenerative disorders will open a new field to develop novel therapies to modulate their levels and/or activity and their harmful effects on the CNS.

show abstract

Section: Klks As Signaling Moleculesmentioning

confidence: 99%

Involvement of Kallikrein-Related Peptidases in Nervous System Disorders

Mella

Figueroa

Otth

et al. 2020

Front. Cell. Neurosci.

View full text Add to dashboard Cite

show abstract

“…A particularly important detail is the target-derived source of NGF (secreted as proNGF; [161]) that cBF neurons encounter, with inhibitory interneurons emerging as the primary source of neuronal NGF. In the cortex, >90% of NGF-labelled cells are interneurons, with less than 3% of pyramidal neurons expressing NGF mRNA [162].…”

Section: Ngf Expression Is Limited To Interneuronsmentioning

confidence: 99%

“…This underpinned the rationale for neurotrophin-based treatments of this condition [196,197], including ongoing clinical trials delivering NGF to the NBM by implant or virus [198,199]. The specific neurotrophin-related changes which occur in AD include down-regulation of BDNF signalling, the accumulation of proNGF in the cortex, and reduced TrkA and TrkB neurotrophic signalling in cBF neurons in association with increased cholinergic dysfunction and cognitive decline (comprehensively reviewed in reference [161]).…”

Section: Neurotrophins and Admentioning

confidence: 99%

Regulation of cholinergic basal forebrain development, connectivity, and function by neurotrophin receptors

et al. 2019

View full text Add to dashboard Cite

Cholinergic basal forebrain (cBF) neurons are defined by their expression of the p75 neurotrophin receptor (p75NTR) and tropomyosin-related kinase (Trk) neurotrophin receptors in addition to cholinergic markers. It is known that the neurotrophins, particularly nerve growth factor (NGF), mediate cholinergic neuronal development and maintenance. However, the role of neurotrophin signalling in regulating adult cBF function is less clear, although in dementia, trophic signalling is reduced and p75NTR mediates neurodegeneration of cBF neurons. Here we review the current understanding of how cBF neurons are regulated by neurotrophins which activate p75NTR and TrkA, B or C to influence the critical role that these neurons play in normal cortical function, particularly higher order cognition. Specifically, we describe the current evidence that neurotrophins regulate the development of basal forebrain neurons and their role in maintaining and modifying mature basal forebrain synaptic and cortical microcircuit connectivity. Understanding the role neurotrophin signalling plays in regulating the precision of cholinergic connectivity will contribute to the understanding of normal cognitive processes and will likely provide additional ideas for designing improved therapies for the treatment of neurological disease in which cholinergic dysfunction has been demonstrated.

show abstract

“…The surface movements of the receptors indicate their activation state (13,14). Although the expression pattern of TrkA and p75 NTR , their interaction and the stimulated signaling pathways leading to AD progression is relatively well known (27,28), their surface movements in AD remained unexplored. Here we showed that both TrkA and p75 NTR exhibit various diffusion modes in healthy hiPSCs and that p75 NTR moves faster along the neurites than TrkA.…”

Section: Discussionmentioning

confidence: 99%

Live cell imaging of single neurotrophin receptor molecules on human neuron in Alzheimer’s disease

Barabás

Kobolák

Godó

et al. 2020

Preprint

View full text Add to dashboard Cite

The changes in the receptor dynamics such as the surface movement of the receptor molecules on the plasma membrane are essential to receptor function. However, whether the receptor dynamics are affected by disease conditions is unknown. Neurotrophin receptors such as TrkA and p75 NTR play a critical role in neuronal survival and their functions are highly affected in Alzheimer's disease (AD). Using live-cell single-molecule imaging of neurotrophin receptors we examined the surface trafficking of TrKA and p75 NTR molecules on human induced pluripotent stem cells (hiPSCs) derived live neurons from presenilin 1 (PSEN1) mutant AD patients and healthy subjects. Here we report that surface trafficking of p75 NTR molecules on neurites is faster than that of TrkA molecules in healthy controls. The surface dynamics of TrkA molecules were elevated in AD patients compared to healthy individuals. In contrast, the surface movement of p75 NTR was significantly smaller in AD patients compared to healthy individuals. Interestingly, amyloid beta1-42 (Aβ1-42) administration increased the surface trafficking of both TrkA and p75 NTR in healthy hiPSCs neurons. These findings provides the first evidence that the surface diffusion of TrkA and p75 NTR molecules are altered in patients suffering from AD. Our data also suggest that Aβ1-42 may responsible for the alteration of the surface movements of TrkA but not for p75 NTR .

show abstract

ProNGF and Neurodegeneration in Alzheimer’s Disease

Cited by 98 publications

References 170 publications

Involvement of Kallikrein-Related Peptidases in Nervous System Disorders

Involvement of Kallikrein-Related Peptidases in Nervous System Disorders

Regulation of cholinergic basal forebrain development, connectivity, and function by neurotrophin receptors

Live cell imaging of single neurotrophin receptor molecules on human neuron in Alzheimer’s disease

Contact Info

Product

Resources

About