Abstract
Progranulin (PGRN) is a multifunctional protein that is widely expressed throughout the brain, where it has been shown to be a critical regulator of CNS inflammation (Ahmed et al., J Neuroinflammation 4:7, 2007; Yin et al., J Exp Med 207:117–128, 2010; Martens et al., J Clin Investig 122:3955–3959; Inestrosa and Arenas). PGRN functions as an autocrine neuronal growth factor, important for long-term neuronal survival (Ahmed et al., J Neuroinflammation 4:7, 2007; Nat Rev Neurosci 11:77–86, 2009). Together, these critical roles in the CNS suggest that enhancing PGRN expression may provide neuronal support and protection for neurodegenerative disorders, such as Parkinson’s disease (PD). Here, we describe the application of PGRN gene transfer using in vivo delivery of lentiviral expression vectors in a rodent model of PD.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
He Z, Bateman A (2003) Progranulin (granulin-epithelin precursor, PC-cell-derived growth factor, acrogranin) mediates tissue repair and tumorigenesis. J Mol Med 81:600–612
Yin F, Banerjee R, Thomas B et al (2010) Exaggerated inflammation, impaired host defense and neuropathology in progranulin-deficient mice. J Exp Med 207:117–128
Martens LH, Zhang J, Barmada SJ et al (2012) Progranulin deficiency promotes neuroinflammation and neuron loss following toxin-induced injury. J Clin Investig 122:3955–3959
Inestrosa NC, Arenas E (2009) Emerging roles of Wnts in the adult nervous system. Nat Rev Neurosci 11:77–86
Ahmed Z, MacKenzie IR, Hutton M et al (2007) Progranulin in frontotemporal lobar degeneration and neuroinflammation. J Neuroinflammation 4:7
Yin F, Dumont M, Banerjee R et al (2010) Behavioral deficits and progressive neuropathology in progranulin-deficient mice: a mouse model of frontotemporal dementia. FASEB J 24:4639–4647
Van Damme P, Van Hoecke A, Lambrechts D et al (2008) Progranulin functions as a neurotrophic factor to regulate neurite outgrowth and enhance neuronal survival. J Cell Biol 181:37–41
Côté M, Poireir A, Aubé B et al (2015) Partial depletion of the proinflammatory monocyte population is neuroprotective in the myenteric plexus but not in the basal ganglia in a MPTP mouse model of Parkinson's disease. Brain Behav Immun 46:154–167
Petkau TL, Neal SJ, Milnerwood A et al (2012) Synaptic dysfunction in progranulin-deficient mice. Neurobiol Dis 45:711–722
Tanaka Y, Chambers JK, Matsuwaki T et al (2014) Possible involvement of lysosomal dysfunction in pathological changes of the brain in aged progranulin-deficient mice. Acta Neuropathol Commun 2:78
Tanaka Y, Matsuwaki T, Yamanouchi K et al (2013) Exacerbated inflammatory responses related to activated microglia after traumatic brain injury in progranulin-deficient mice. Neuroscience 231:49–60
Tasker RA, Adams-Marriott AL, Shaw CA (2010) New animal models of progressive neurodegeneration: tools for identifying targets in predictive diagnostics and presymptomatic treatment. EPMA J 1:217–227
Xu J, Xilouri M, Bruban J et al (2011) Extracellular progranulin protects cortical neurons from toxic insults by activating survival signaling. Neurobiol Aging 32:2326.e5–2326.16
Ryan CL, Baranowski DC, Chitramuthu BP et al (2009) Progranulin is expressed within motor neurons and promotes neuronal cell survival. BMC Neurosci 10:130
Kanazawa M, Kawamura K, Takahashi T et al (2015) Multiple therapeutic effects of progranulin on experimental acute ischaemic stroke. Brain 138:1932–1948
Van Kampen JM, Baranowski DB, Kay DG (2014) Progranulin gene delivery protects dopaminergic neurons in a mouse model of Parkinson's disease. PLoS One 9:e97032
Kantor B, Bailey R, Wimberly K et al (2014) Methods for gene transfer to the central nervous system. Adv Genet 87:125–197
Kordower JH, Emborg ME, Bloch J et al (2000) Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease. Science 290:767–773
Manfredsson FP (2016) Introduction to viral vectors and other delivery methods for gene therapy of the nervous system. Methods Mol Biol 1382:3–18
Naldini L, Blomer U, Gage FH et al (1996) Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector. Proc Natl Acad Sci U S A 93:11382–11388
Kordower JH, Bloch J, Ma SY et al (1999) Lentiviral gene transfer to the nonhuman primate brain. Exp Neurol 160:1–16
Jakobsson J, Ericson C, Jansson M et al (2003) Targeted trans-gene expression in rat brain using lentiviral vectors. J Neurosci Res 73:876–885
Franklin K, Paxinos G (2008) The mouse brain in stereotaxic coordinates, 3rd edn. Academic Press
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Van Kampen, J.M. (2018). Methods to Investigate the Protection Against Neurodegenerative Disorders Provided by Progranulin Gene Transfer in the Brain. In: Bateman, A., Bennett, H., Cheung, S. (eds) Progranulin. Methods in Molecular Biology, vol 1806. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8559-3_17
Download citation
DOI: https://doi.org/10.1007/978-1-4939-8559-3_17
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-8557-9
Online ISBN: 978-1-4939-8559-3
eBook Packages: Springer Protocols