Methods to Investigate the Protection Against Neurodegenerative Disorders Provided by Progranulin Gene Transfer in the Brain.

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.