MinireviewThe amyloid precursor protein and postnatal neurogenesis/neuroregeneration
Section snippets
APP and proliferation of adult neural progenitors at the subventricular zone
The non-amyloidogenic sAPP had been implicated in enhancement of synaptogenesis, neurite outgrowth, and neuronal survival. In particular, sAPP has been known for some time now to be able to stimulate the proliferation of neural progenitor cells in culture [21], [22], as does the ectodomain of APLP-2 [23]. A possible role for the N-terminus of APP in stem cell growth has received support in that crystal structure analysis at 1.8 Å resolution of the cysteine-rich N-terminal heparin-binding domain
APP, postdevelopmental neurite arborization and neuronal regeneration after injury
It is amazing how much we have learned about various aspects of nervous system development from invertebrate models. In a recent report, Leyssen et al. [42] had, however, used a Drosophila model to unveil a postnatal function of APP. The neurons they focused on are sLNv, a well-characterized group of Drosophila brain neurons which regulates circadian rhythm. These have a simple and stereotypical morphology and therefore allowed high resolution microscopic analysis of axonal arborization
Epilogue
The evolutionary conservation of the APP and related genes is best explained by their products serving an important developmental or postnatal function. Genetic analysis clearly illustrates, in spite of obvious redundancy, the importance of APP and APLPs in postnatal function. The in vivo studies discussed here opened up new avenues to further explore the role of APP family members in postnatal neurogenesis as well as axonal regeneration after injury. Of course, attempts to study endogenous,
Acknowledgments
Work on neuronal death and regeneration in BLT’s laboratory is supported by research Grant No. 03/1/21/19/247 from the Agency for Science, Technology and Research (A*STAR)’s Biomedical Research council (BMRC).
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2022, NeuroscienceCitation Excerpt :As the most prevalent form of dementia, mostly associated with aging, AD is projected to increase its social and economic burden in the next decades, especially in less developed countries. The AD hallmarks include extracellular senile plaques composed mainly by amyloid-β (Aβ) peptides varying in length mainly from 39 to 43 amino acids (aa), produced by the sequential cleavage of the amyloid precursor protein (APP) by β and γ secretases (Chen and Tang, 2006; Li et al., 2018). Monomeric Aβ peptides tend to associate into oligomer intermediates of varied sizes and to progress to larger supramolecular structures such as fibrils and plaques (Hortschansky et al., 2005; Cohen et al., 2013).
Neurogenesis in aging and age-related neurodegenerative diseases
2022, Ageing Research ReviewsThe Neuropathology and Neurobiology of Traumatic Brain Injury
2012, NeuronCitation Excerpt :Intra-axonal APP accumulation is an established marker for DAI and is the gold standard to identify DAI in routine forensic medicine, for example, in deaths from motor vehicle accidents and suspected shaken baby syndrome (Gleckman et al., 1999; Gorrie et al., 2002). The increase in APP expression after DAI is probably related to the proposed role of APP for promoting axonal outgrowth after injury (Chen and Tang, 2006). Data from studies of brain trauma in humans and on experimental rotational brain trauma in animals indicate that DAI is a long-term process in which axons continue to degenerate and swell during an extended period.
Neuroprotective profile of the multitarget drug rasagiline in Parkinson's disease
2011, International Review of NeurobiologyCitation Excerpt :ii) In the nonamyloidogenic pathway, APP is cleaved by α-secretase, within the Aβ sequence and generates a secreted form of soluble APP (sAPPα), thus precluding the formation of the amyloidogenic Aβ (Vetrivel and Thinakaran, 2006). Secreted sAPPα has been implicated to possess neurotrophic and neuroprotective properties (Chen and Tang, 2006; Chow et al., 2010; Hampel et al., 2010). Available evidence has demonstrated that α-secretase activity could be regulated via PKC, MAPK, and TK receptor signaling pathways, calcium ion (Ca2+), and hormonal signaling (Mills and Reiner, 1999a,b; Zhang and Xu, 2007).
A novel anti-Alzheimer's disease drug, ladostigil. neuroprotective, multimodal brain-selective monoamine oxidase and cholinesterase inhibitor
2011, International Review of NeurobiologyCitation Excerpt :The precise mechanisms leading to neurodegeneration in AD are not completely clear; however, most studies have focused on the role of Aβ–APP and its products in AD pathogenesis (Zhang and Xu, 2007). Secreted sAPPα has been implicated to possess neurotrophic and neuroprotective properties, and Aβ peptides exert contrasting effects on neuronal survival (Chen and Tang, 2006; Chow et al., 2010). Available evidence has demonstrated that α-secretase activity could be regulated via PKC, calcium ion (Ca2+), tyrosine kinase (TK), MAPK, and hormonal signaling (Mills and Reiner, 1999a,b; Zhang and Xu, 2007).