ArticleJournal of Alzheimer's disease : JAD2017
TFP5, a Peptide Inhibitor of Aberrant and Hyperactive Cdk5/p25, Attenuates Pathological Phenotypes and Restores Synaptic Function in CK-p25Tg Mice.
Article in Journal of Alzheimer's disease : JAD, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 40 citations in OpenAlex.
- The Duality of Cdk5: A Master Regulator in Neurodevelopment and a Hijacked Oncogene in Cancer.Cells · 2025Review
- Targeting a Tau Kinase Cdk5, Cyclin-Dependent Kinase: A Blood-Based Diagnostic Marker and Therapeutic Earmark for Alzheimer's Disease.Biomolecules · 2025Article
- Article
- A Retrospective Tribute to Dr. Harish Pant (1938-2023) and His Seminal Work on Cyclin Dependent Kinase 5.Neurochemical research · 2024Article
- S-Nitrosylation of p39 promotes its degradation and contributes to synaptic dysfunction induced by β-amyloid peptide.Communications biology · 2024Article
- A Cdk5-derived peptide inhibits Cdk5/p25 activity and improves neurodegenerative phenotypes.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The regulation of neuronal autophagy and cell survival by MCL1 in Alzheimer's disease.Acta materia medica · 2022Article
- Focusing on cyclin-dependent kinases 5: A potential target for neurological disorders.Frontiers in molecular neuroscience · 2022Review
- The role of Cdk5 in neurological disorders.Frontiers in cellular neuroscience · 2022Review
- Three decades of Cdk5.Journal of biomedical science · 2021Review
- When Good Kinases Go Rogue: GSK3, p38 MAPK and CDKs as Therapeutic Targets for Alzheimer's and Huntington's Disease.International journal of molecular sciences · 2021Review
- Metformin Ameliorates Synaptic Defects in a Mouse Model of AD by Inhibiting Cdk5 Activity.Frontiers in cellular neuroscience · 2020Article
- Article
- Overexpression of the Cdk5 inhibitory peptide in motor neurons rescue of amyotrophic lateral sclerosis phenotype in a mouse model.Human molecular genetics · 2019Article
- Multifaceted Regulation of ALDH1A1 by Cdk5 in Alzheimer's Disease Pathogenesis.Molecular neurobiology · 2019Article
- Phospho-Tau Bar Code: Analysis of Phosphoisotypes of Tau and Its Application to Tauopathy.Frontiers in neuroscience · 2018Review
- The Cdk5-Mcl-1 axis promotes mitochondrial dysfunction and neurodegeneration in a model of Alzheimer's disease.Journal of cell science · 2017Article
- Curcumin Ameliorates Neuroinflammation, Neurodegeneration, and Memory Deficits in p25 Transgenic Mouse Model that Bears Hallmarks of Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2017Article
- Cyclin-Dependent Kinase 5 Regulates cPLA2 Activity and Neuroinflammation in Parkinson's Disease.eNeuroArticle
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
It has been reported that cyclin-dependent kinase 5 (cdk5), a critical neuronal kinase, is hyperactivated in Alzheimer's disease (AD) and may be, in part, responsible for the hallmark pathology of amyloid plaques and neurofibrillary tangles (NFTs). It has been proposed by several laboratories that hyperactive cdk5 results from the overexpression of p25 (a truncated fragment of p35, the normal cdk5 regulator), which, when complexed to cdk5, induces hyperactivity, hyperphosphorylated tau/NFTs, amyloid-β plaques, and neuronal death. It has previously been shown that intraperitoneal (i.p.) injections of a modified truncated 24-aa peptide (TFP5), derived from the cdk5 activator p35, penetrated the blood-brain barrier and significantly rescued AD-like pathology in 5XFAD model mice. The principal pathology in the 5XFAD mutant, however, is extensive amyloid plaques; hence, as a proof of concept, we believe it is essential to demonstrate the peptide's efficacy in a mouse model expressing high levels of p25, such as the inducible CK-p25Tg model mouse that overexpresses p25 in CamKII positive neurons. Using a modified TFP5 treatment, here we show that peptide i.p. injections in these mice decrease cdk5 hyperactivity, tau, neurofilament-M/H hyperphosphorylation, and restore synaptic function and behavior (i.e., spatial working memory, motor deficit using Rota-rod). It is noteworthy that TFP5 does not inhibit endogenous cdk5/p35 activity, nor other cdks in vivo suggesting it might have no toxic side effects, and may serve as an excellent therapeutic candidate for neurodegenerative disorders expressing abnormally high brain levels of p25 and hyperactive cdk5.
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