The Emerging Role of the Molecular Chaperone Clusterin in Parkinson’s Disease

Clusterin (CLU) is a heterodimeric, ATP-independent molecular chaperone that exhibits high expression in the brain. While CLU primarily functions in the extracellular environment, its chaperone activity in the intracellular compartment under different stress conditions, as well as its involvement in various signaling networks, has been demonstrated. CLU has been extensively associated with Alzheimer's Disease; however, increasing evidence links this chaperone to Parkinson's Disease (PD) as well. Thus, in this review we will discuss evidence concerning the involvement of CLU in the pathogenesis of PD with a particular focus on molecular mechanisms leading to the formation and the spreading of alpha-Synuclein (alpha-Syn) aggregates. Specifically, the role of CLU will be discussed in neurons and in glial cells, taking into account that the neuron-glia cross-talk is an essential and dynamic interplay that is compromised in neurodegenerative disorders. Moreover, the possible role of CLU as a biomarker in different biological fluids, such as cerebrospinal fluid, plasma, and serum, and its therapeutic potential will be addressed. In this regard, the past years have seen huge efforts to discover molecules able to mitigate alpha-Syn burden and its related toxicity. Overall, this overview highlights CLU as an intriguing target that can affect biochemical events underlying PD pathology.