Journal Article

DZNE-2026-00890

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Analysis of PTEN Antagonistic Peptides (PAPs) in Neuronal Growth and Traumatic Brain Injury (TBI).

Rivera, K. K. ; Tsai, Y.-L. ; Song, J. ; Gu, H. ; Gutt, A.-S. ; Sinske, D. ; Klugmann, C. ; Pagliarini, M.DZNE* ; Roselli, F.DZNE* ; Synatschke, C. V. ; Knöll, B.

2026
American Chemical Soc. Columbus, Ohio

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Please use a persistent id in citations: doi:10.1021/acs.biomac.6c00695

Abstract: PTEN (phosphatase and tensin homologue) is an established cellular growth brake whose inhibition stimulates regeneration of injured neurons in rodent models. Herein, we employed peptide-based PTEN inhibition targeting PTEN's phosphatase activity. Therefore, a fusion peptide (PAP2-TAT) of PAP2 (PTEN antagonistic peptide 2) with TAT (transactivator of transcription) was used to enable cellular entry. PAP2-TAT was not cytotoxic and entered the cytoplasm of primary mouse neurons, where it enhanced neurite growth, growth cone size, and synaptophysin abundance. PAP2-TAT modestly elevated P-AKT and more strongly elevated P-ERK levels. Furthermore, STATs (signal transducer and activator of transcription) were phosphorylated after PAP2-TAT administration. So far, PAPs have not been employed in traumatic brain injury (TBI). In a mouse TBI model, a single PAP2-TAT injection improved single parameters of gait impairments but had no impact on neuroinflammation and TBI-associated weight loss. In summary, peptide-based PTEN inhibition aids neuronal cell growth and regeneration after brain injury.

Keyword(s): Animals (MeSH) ; PTEN Phosphohydrolase: antagonists & inhibitors (MeSH) ; PTEN Phosphohydrolase: metabolism (MeSH) ; Brain Injuries, Traumatic: drug therapy (MeSH) ; Brain Injuries, Traumatic: pathology (MeSH) ; Brain Injuries, Traumatic: metabolism (MeSH) ; Mice (MeSH) ; Peptides: pharmacology (MeSH) ; Peptides: chemistry (MeSH) ; Neurons: drug effects (MeSH) ; Neurons: metabolism (MeSH) ; Neurons: pathology (MeSH) ; Male (MeSH) ; Mice, Inbred C57BL (MeSH) ; PTEN Phosphohydrolase ; Peptides ; Pten protein, mouse

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Contributing Institute(s):

1. Metabolic Changes in Neurodegeneration (AG Roselli)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2026

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; Index Chemicus ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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