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Review
. 2022 May;247(9):779-787.
doi: 10.1177/15353702221081022. Epub 2022 Mar 7.

Dysregulation of multiple signaling pathways: A possible cause of cerebral palsy

Jyoti Upadhyay  1 , Mohd Nazam Ansari  2 , Abdul Samad  3 , Ashutosh Sayana  4
Affiliations
Review

Dysregulation of multiple signaling pathways: A possible cause of cerebral palsy

Jyoti Upadhyay et al. Exp Biol Med (Maywood). 2022 May.

Abstract

Cerebral palsy (CP) is a lifelong disability characterized by the impairment of brain functions that result in improper posture and abnormal motor patterns. Understanding this brain abnormality and the role of genetic, epigenetic, and non-genetic factors such as signaling pathway dysregulation and cytokine dysregulation in the pathogenesis of CP is a complex process. Hypoxic-ischemic injury and prematurity are two well-known contributors of CP. Like in the case of other neurodevelopmental disorders such as intellectual disability and autism, the genomic constituents in CP are highly complex. The neuroinflammation that is triggered by maternal cytokine response plays a critical role in the pathogenesis of fetal inflammation response, which is one of the contributing factors of CP, and it continues even after the birth of children suffering from CP. Canonical Wnt signaling pathway is important for the development of mammalian fetal brain and it regulates distinct processes including neurogenesis. The glycogen synthase kinase-3 (GSK-3) antagonistic activity in the Wnt signaling pathway plays a crucial role in neurogenesis and neural development. In this review, we investigated several genetic and non-genetic pathways that are involved in the pathogenesis of CP and their regulation, impairment, and implications for causing CP during embryonic growth and developmental period. Investigating the role of these pathways help to develop novel therapeutic interventions and biomarkers for early diagnosis and treatment. This review also helps us to comprehend the mechanical approach of various signaling pathways, as well as their consequences and relevance in the understanding of CP.

Keywords: Cerebral palsy; Wnt signaling pathway; cytokine regulation; epigenetics; genetics.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Genetic implications in cerebral palsy showing main sites and types. (A color version of this figure is available in the online journal.)
Figure 2.
Figure 2.
Association of cytokines, reactive oxygen species, and maternal infection and inflammation that causes microglial activation to the prematurity and periventricular leukomalacia that are responsible for cerebral palsy. (A color version of this figure is available in the online journal.)
Figure 3.
Figure 3.
GSK-3 regulations of Wnt and Akt signaling pathways. (A color version of this figure is available in the online journal.)
See this image and copyright information in PMC

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References

    1. Bax M, Goldstein M, Rosenbaum P, Leviton A, Paneth N, Dan B, Jacobsson B, Damiano D. Executive Committee for the definition of cerebral palsy. Proposed definition and classification of cerebral palsy, April 2005. Dev Med Child Neurol 2005;47:571–6 - PubMed
    1. Ellenberg JH, Nelson KB. The association of cerebral palsy with birth asphyxia: a definitional quagmire. Dev Med Child Neurol 2013;55:210–6 - PubMed
    1. Paneth N, Hong T, Korzeniewski S. The descriptive epidemiology of cerebral palsy. Clin Perinatol 2006;33:251–67 - PubMed
    1. Hagberg H, Gressens P, Mallard C. Inflammation during fetal and neonatal life: implications for neurologic and neuropsychiatric disease in children and adults. Ann Neurol 2012;71:444–57 - PubMed
    1. Badawi N, Felix JF, Kurinczuk JJ, Dixon G, Watson L, Keogh JM, Valentine J, Stanley FJ. Cerebral palsy following term newborn encephalopathy: a population-based study. Dev Med Child Neurol 2005;47:293–8 - PubMed