Chondroitin sulfate proteoglycans are a common component of neuronal inclusions and astrocytic reaction in neurodegenerative diseases

“Targeting astrocytes in CNS injury and disease: A translational research approach”

“…Astrocytes have been shown to dramatically alter microglial behavior in response to amyloid plaques (DeWitt et al, 1998a). When astrocytes respond vigorously to aggregated amyloid, they surround the plaque and further seclude it by synthesizing a CSPG rich matrix (Canning et al, 1993; DeWitt and Silver, 1996; DeWitt et al, 1993, 1994, 1998b). Such reactive astrocyte activity, in turn, helps to shield the plaque from an aggressive engulfment by microglia, which increases the presence of plaque material within the brain.…”

Inhibitors of myelination: ECM changes, CSPGs and PTPs

“…Reactive glial cells, in particular astrocytes and microglia, contribute to formation of the so-called ‘glial scar’, by depositing extracellular matrix proteins and upregulating molecules that are often inhibitory to regeneration (Fitch and Silver, 2008; Galtrey et al, 2008; Morgenstern et al, 2002; Rhodes and Fawcett, 2004; Sherman and Back, 2008). High levels of chondroitin sulfate proteoglycans (CSPGs) are present in the scar after many types of CNS insults including spinal cord injury (SCI; Jones et al, 2003; Lemons et al, 1999; McTigue et al, 2001; Tang et al, 2003), epilepsy (Kurazono et al, 2001; Okamoto et al, 2003), Alzheimer's disease (DeWitt et al., 1993; Snow et al, 1988; 1990), Parkinson's disease (DeWitt et al, 1994), stroke (Carmichael et al, 2005; Deguchi et al, 2005) and multiple sclerosis (MS; Mohan et al, 2010; Sobel, 2001; Sobel and Ahmed, 2001). Deposition of CSPGs post-injury may be a protective CNS response that contains the damage and spares intact tissue from further injury (Galtrey and Fawcett, 2007; Silver and Miller, 2004; Yiu and He, 2006).…”

“…Fibronectin does not appear to impede remyelination unless it forms aggregates, which occurs in MS lesions but not in toxin-induced demyelination (Stoffels et al, 2013; Zhao et al, 2009). In active, but not chronic, demyelinated MS lesions, dystrophic, demyelinated axons, astrocytes and the microvasculature also express vitronectin (DeWitt et al, 1994; Sobel et al, 1995). …”

Modulation of BACE1 Activity as a Potential Therapeutic Strategy for Treating Alzheimer’s Disease

“…GAGs are long, linear polysaccharides that can be covalently attached to a proteinaceous core to form PGs [34,120]. Since this initial discovery, PGs have been found in deposits associated with other amyloidoses, including Parkinson's disease [126], familial amyloidotic polyneuropathy [127,128], familial British dementia [129], familial Danish dementia [129], the prion diseases Creutzfeld-Jakob disease and Gerstmann-Sträussler-Scheinker syndrome [130], dementia with Lewy bodies [126] and progressive supranuclear palsy [126]. Several studies conducted in the 1980s and 1990s demonstrated that both heparin sulfate proteoglycans (HSPGs) and chondroitin sulfate proteoglycans (CSPGs) are constituents of both diffuse and neuritic plaques in the AD brain [121][122][123][124][125].…”