The Pak1 Kinase: An Important Regulator of Neuronal Morphology and Function in the Developing Forebrain
Abstract
The mammalian central nervous system (CNS) represents a highly complex unit, the correct function of which relies on the appropriate differentiation and survival of its neurones. It is becoming apparent that the Rho family of small GTPases and their downstream targets have a major function in regulating CNS development. Among the effectors, the role of the Pak family of kinases, especially Pak1, is becoming increasingly evident. Although highest levels of Pak1 expression and activation are detected in the developing nervous system, much remains undiscovered concerning its function in neurones. This review summarises what is currently known regarding the biological and molecular role of Pak1 in the mammalian forebrain. It emphasises the importance of Pak1 in regulating neuronal polarity, morphology, migration and synaptic function. Consequently, there are also strong indications that Pak1 is required for normal cognitive function. Furthermore, loss of Pak1 has been associated with the progression of neurodegenerative disorders, particularly Alzheimer's disease, while up-regulation and de-regulation may be responsible for oncogenic transformation of support cells within the CNS, especially astrocyte progenitors. Together, these new and exciting findings encourage the future exploration into the function of Pak1 in the nervous system, thus, paving the way for novel strategies towards improved diagnosis and therapeutic treatment of diseases that affect the CNS.
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Rock and Pak are two kinases that can be activated respectively by Rho and Cdc42.
“Amongst known effectors of Rho and Cdc42, Rock and Pak are two kinases that can be activated repsectively by these GTPases24–26.”
From Local, persistent activation of Rho GTPases during plasticity of single dendritic spines (2011) · cites this paper as [24]
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- Authors
- Nikolić, M.
- Affiliations
- Imperial College London (GB)
- Corresponding author
- Nikolić, Margareta
- ORCID
- Nikolić, Margareta
- Venue
- Molecular Neurobiology
- Published
- 2008-06
- Volume
- 37
- Issue
- 2-3
- Pages
- 187-202
- ISSN
- 0893-7648 (ISSN-L)
- 1559-1182
- OpenAlex
- W2027848727
- Cited by
- 56
- References
- 9
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 1 · 2018: 3 · 2016: 3 · 2015: 2 · 2014: 4 · 2013: 7 · 2012: 3
- FWCI
- 1.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular Neurobiology (publishedVersion)
- PubMed (publishedVersion)
- University of Hertfordshire Research Archive (University of Hertfordshire) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- Rho GTPases, neuronal polarity, neuronal morphology, neuronal migration, synaptic function, forebrain development, cognitive function, Alzheimer's disease, neurodegeneration, oncogenic transformation, central nervous system development
- MeSH terms
- Animals, Cognition, Enzyme Activation, Humans, Neurons, Stem Cells, Signal Transduction, Central Nervous System Neoplasms, Prosencephalon, Cell Polarity, Neurodegenerative Diseases, Cell Proliferation, p21-Activated Kinases
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