FIGURE 2 | Neuroinflammation — the point of convergence for distinct neurodegenerative disorders.

Chronic microglial activation and macrophage infiltration are prominent features in the CNS of patients and mouse models with the gangliosidoses and non-lysosomal storage disorders — namely, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease and prion diseases (see also Box 3). Activated resident microglial cells and recruited macrophages that cross the blood–brain barrier (BBB) generate oxygen-free radicals, nitric oxide and other potentially toxic products, such as cytokines. This leads to chronic inflammation, which is accompanied by oxidative stress — a process that parallels disease progression in animal models of both lysosomal storage disorders and more common neurodegenerative diseases. Although these diseases have distinct pathogenic causes that lead to microglial activation, the mechanisms that contribute to neurodegenerative processes, such as neuronal dysfunction and apoptosis, are not exclusive to each disorder; for example, altered calcium homeostasis is another common feature of many lysosomal storage disorders and more common neurodegenerative diseases.

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