The Expanding Universe of Neurotrophic Factors: Therapeutic Potential in Aging and Age-Associated Disorders

Lanni, Cristina; Stanga, Serena; Racchi, Marco; Govoni, Stefano

doi:10.2174/138161210790883741

Cited by 48 publications

(49 citation statements)

References 270 publications

(296 reference statements)

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“…This is the first study to demonstrate that the neuroprotective mechanism of CAPE might also involve the induction of neuritogenesis. It is known that the levels of neurotrophic factors or their receptors are altered in neurodegenerative diseases and therefore, neurotrophic factors have been suggested as potential candidates of treatment for such diseases (Levy et al, 2005;Lanni et al, 2010). However, neurotrophic factors, including NGF, are not able to cross the blood brain barrier (Lin et al, 2010a).…”

Section: Discussionmentioning

confidence: 99%

Caffeic acid phenethyl ester (CAPE) protects PC12 cells from MPP+ toxicity by inducing the expression of neuron-typical proteins

et al. 2014

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Neurite loss is an early event in neurodegenerative diseases; therefore, the regeneration of the network of neurites constitutes an interesting strategy of treatment for such disorders. Neurotrophic factors play a critical role in neuronal regeneration, but their clinical use is limited by their inability to cross the blood brain barrier. Oxidative and inflammatory events are implicated in neurodegeneration and antioxidant compounds have been suggested as potential neuroprotectors. The protective potential of CAPE (caffeic acid phenethyl ester) has been shown in different models of neurotoxicity (in vitro and in vivo) and it has been associated with immune-modulatory, antioxidant and anti-inflammatory properties; however, other mechanisms might be involved. The present study demonstrates that CAPE protects PC12 cells from the cellular death induced by the dopaminergic neurotoxin MPP(+) by increasing the network of neurites. Results showed that CAPE induced the formation, elongation and ramification of neurites in PC12 cells non-stimulated with NGF (nerve growth factor) and inhibited the shortage of neurites induced by the dopaminergic neurotoxin. These effects were associated with increased expression of neuron-typical proteins responsible for axonal growth (GAP-43) and synaptogenesis (synaptophysin and synapsin I). It is noteworthy that, unlike neurotrophins, CAPE would be able to cross the blood brain barrier and exert its neurotrophic effects in the brain. This study corroborates the therapeutic potential of CAPE in neurodegenerative diseases while proposes the involvement of neuroplasticity in the mechanism of neuroprotection.

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Section: Discussionmentioning

confidence: 99%

Caffeic acid phenethyl ester (CAPE) protects PC12 cells from MPP+ toxicity by inducing the expression of neuron-typical proteins

et al. 2014

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“…NTFs have been shown to promote the survival of specific populations of brain neurons under experimental conditions relevant to brain aging and neurodegenerative disorders. NTFs exert their effects on the development and function of neurons by binding to cell surface receptors possessing intrinsic tyrosine kinase activity, in turn activating down-stream kinases including the phosphatidylinositol-3-kinase, protein kinase C , and the mitogenactivated protein kinase, as well as several small G-proteins [53,54]. As a consequence, some transcription factors are activated and ultimately the expression of genes that encode proteins involved in regulating neuronal survival, differentiation and plasticity is induced.…”

Section: Neurodegenerationmentioning

confidence: 99%

“…As a consequence, some transcription factors are activated and ultimately the expression of genes that encode proteins involved in regulating neuronal survival, differentiation and plasticity is induced. Cellular and molecular mechanisms by which neurotrophic factors may influence cell survival and excitability are also critically examined to provide novel concepts and targets for the treatment of physiological changes bearing detrimental functional alterations and of different diseases affecting the central nervous system during ageing [53].…”

Section: Neurodegenerationmentioning

confidence: 99%

Low Grade Inflammation as a Common Pathogenetic Denominator in Age-Related Diseases: Novel Drug Targets for Anti-Ageing Strategies and Successful Ageing Achievement

Candore

Caruso

Jirillo³

et al. 2010

CPD

127

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Nowadays, people are living much longer than they used to do, however they are not free from ageing. Ageing, an inexorable intrinsic process that affects all cells, tissues, organs and individuals, is a post-maturational process that, due to a diminished homeostasis and increased organism frailty, causes a reduction of the response to environmental stimuli and, in general, is associated to an increased predisposition to illness and death. However, the high incidence of death due to infectious, cardiovascular and cancer diseases underlies a common feature in these pathologies that is represented by dysregulation of both instructive and innate immunity. Several studies show that a low-grade systemic inflammation characterizes ageing and that inflammatory markers are significant predictors of mortality in old humans. This pro-inflammatory status of the elderly underlies biological mechanisms responsible for physical function decline and agerelated diseases such as Alzheimer's disease and atherosclerosis are initiated or worsened by systemic inflammation. Understanding of the ageing process should have a prominent role in new strategies for extending the health old population. Accordingly, as extensively discussed in the review and in the accompanying related papers, investigating ageing pathophysiology, particularly disentangling agerelated low grade inflammation, is likely to provide important clues about how to develop drugs that can slow or delay ageing.

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“…Some authors regard depression as a disease of abnormal trophic support [3]. Neurotrophic factors (NTFs), along with cytokines, play an important role in supporting brain equilibrium in stressogenic situations and are central to many aspects of the nervous system function.…”

Section: Introductionmentioning

confidence: 99%

Rodent Models of Depression: Neurotrophic and Neuroinflammatory Biomarkers

Stepanichev

Дыгало

Grigoryan

et al. 2014

BioMed Research International

148

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Rodent models are an indispensable tool for studying etiology and progress of depression. Since interrelated systems of neurotrophic factors and cytokines comprise major regulatory mechanisms controlling normal brain plasticity, impairments of these systems form the basis for development of cerebral pathologies, including mental diseases. The present review focuses on the numerous experimental rodent models of depression induced by different stress factors (exteroceptive and interoceptive) during early life (including prenatal period) or adulthood, giving emphasis to the data on the changes of neurotrophic factors and neuroinflammatory indices in the brain. These parameters are closely related to behavioral depression-like symptoms and impairments of neuronal plasticity and are both gender- and genotype-dependent. Stress-related changes in expression of neurotrophins and cytokines in rodent brain are region-specific. Some contradictory data reported by different groups may be a consequence of differences of stress paradigms or their realization in different laboratories. Like all experimental models, stress-induced depression-like conditions are experimental simplification of clinical depression states; however, they are suitable for understanding the involvement of neurotrophic factors and cytokines in the pathogenesis of the disease—a goal unachievable in the clinical reality. These major regulatory systems may be important targets for therapeutic measures as well as for development of drugs for treatment of depression states.

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The Expanding Universe of Neurotrophic Factors: Therapeutic Potential in Aging and Age-Associated Disorders

Cited by 48 publications

References 270 publications

Caffeic acid phenethyl ester (CAPE) protects PC12 cells from MPP+ toxicity by inducing the expression of neuron-typical proteins

Caffeic acid phenethyl ester (CAPE) protects PC12 cells from MPP+ toxicity by inducing the expression of neuron-typical proteins

Low Grade Inflammation as a Common Pathogenetic Denominator in Age-Related Diseases: Novel Drug Targets for Anti-Ageing Strategies and Successful Ageing Achievement

Rodent Models of Depression: Neurotrophic and Neuroinflammatory Biomarkers

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