The role of caspases in Alzheimer’s disease; potential novel therapeutic opportunities

Rohn, Troy T.

doi:10.1007/s10495-010-0463-2

Cited by 99 publications

(69 citation statements)

References 49 publications

(48 reference statements)

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“…It has been reported that in vivo minocycline treatment in transgenic mice over expressing human tau, results in reduced phosphorylation of tau and its cleavage by caspase 3 [39]. This compound exhibits its activity against AD associated reactive microgliosis [3,40]. As a whole, minocycline is proving itself as an upcoming promising compound for the treatment of AD.…”

Section: Evidence That Caspases As Therapeutic Targets In the Treatmementioning

confidence: 98%

“…Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterized by extensive neuronal loss leading to confusion, disturbances in short term memory, cognitive impairment and dementia [1][2][3]. AD is diagnosed based on the extent of senile plaques composed of beta-amyloid (Aβ) and neurofibrillary tangles (NFTs) along with neuron loss [1,2].…”

Section: Introductionmentioning

confidence: 99%

“…NFTs consist of Paired Helical Filaments (PHF) resulting from the hyper-phosphorylation of the microtubule-binding protein tau. Tau plays an essential role in maintaining microtubule stability and in AD, neuronal tau is strangely phosphorylated and proteolyzed resulting in an impairment of the normal functions of tau [1][2][3]. In addition to NFTs, the other players of senile plaques primarily composed of extracellular amyloid-β (Aβ).…”

Section: Introductionmentioning

confidence: 99%

“…Subsequent formation, Aβ is selfaggregated into insoluble β-sheet structures that lead to the formation of extracellular plaques. The deposition of Aβ is an early event in the pathogenesis of AD that precedes the formation of NFTs and collectively is referred to as the beta-amyloid hypothesis [3,4]. Even though the presence of both plaques and tangles are central features associated with AD, but the link between these two characteristic pathologies has remained elusive.…”

Section: Introductionmentioning

confidence: 99%

“…The cleavage of these proteins may result in the breakdown of the cytoskeleton while the cleavage of tau may facilitate its hyperphosphorylation, leading to further instability in the cytoskeleton. Recent evidence suggests that caspases may be playing a vital role in the disease mechanisms underlying AD including promoting Aβ formation as well as linking plaques to NFTs [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

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Caspases: A Potential Therapeutic Targets in the Treatment of Alzheimer’s Disease

Jana¹

2013

Transl Med

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An enormous body of evidence supports the activation of caspases may be responsible for the neurodegeneration associated with Alzheimer's disease (AD) and for that reason, caspases are potential therapeutic targets for the management of this disorder. However, till date, the studies testing with prospective role of caspase inhibitors for the treatment of AD have yet to be realized. Obviously, this is due to the potential side effects due to long term use of caspase inhibitors. In addition, a further assessment is warned in relation to the therapeutic efficacy and stress of targeting caspase inhibition with the potential caspase inhibitors and its improved delivery system to the brain in the treatment of AD.

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Section: Evidence That Caspases As Therapeutic Targets In the Treatmementioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Caspases: A Potential Therapeutic Targets in the Treatment of Alzheimer’s Disease

Jana¹

2013

Transl Med

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Cell death proteins: An evolutionary role in cellular adaptation before the advent of apoptosis

Dick

Megeney

2013

BioEssays

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Programmed cell death (PCD) or apoptosis is a broadly conserved phenomenon in metazoans, whereby activation of canonical signal pathways induces an ordered dismantling and death of a cell. Paradoxically, the constituent proteins and pathways of PCD (most notably the metacaspase/caspase protease mediated signal pathways) have been demonstrated to retain non-death functions across all phyla including yeast, nematodes, drosophila, and mammals. The ancient conservation of both death and non-death functions of PCD proteins raises an interesting evolutionary conundrum: was the primordial intent of these factors to induce cell death or to regulate other cellular adaptations? Here, we propose the hypothesis that apoptotic behavior of PCD proteins evolved or were co-opted from core non-death functions.

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Apoptosis and its therapeutic implications in neurodegenerative diseases

Erekat

2021

Clinical Anatomy

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Neurodegenerative disorders are characterized by progressive loss of particular populations of neurons. Apoptosis has been implicated in the pathogenesis of neurodegenerative diseases, including Parkinson disease, Alzheimer disease, Huntington disease, and amyotrophic lateral sclerosis. In this review, we focus on the existing notions relevant to comprehending the apoptotic death process, including the morphological features, mediators and regulators of cellular apoptosis. We also highlight the evidence of neuronal apoptotic death in Parkinson disease, Alzheimer disease, Huntington disease, and amyotrophic lateral sclerosis. Additionally, we present evidence of potential therapeutic agents that could modify the apoptotic pathway in the aforementioned neurodegenerative diseases and delay disease progression. Finally, we review the clinical trials that were conducted to evaluate the use of anti-apoptotic drugs in the treatment of the aforementioned neurodegenerative diseases, in order to highlight the essential need for early detection and intervention of neurodegenerative diseases in humans.

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The role of caspases in Alzheimer’s disease; potential novel therapeutic opportunities

Cited by 99 publications

References 49 publications

Caspases: A Potential Therapeutic Targets in the Treatment of Alzheimer’s Disease

Caspases: A Potential Therapeutic Targets in the Treatment of Alzheimer’s Disease

Cell death proteins: An evolutionary role in cellular adaptation before the advent of apoptosis

Apoptosis and its therapeutic implications in neurodegenerative diseases

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