Matrix metalloproteinases and related proteins in Alzheimer's disease, Parkinson's disease and other neurodegenerative disorders

The main neurodegenerative diseases can be loosely grouped into two broad categories - memory disorders or 'dementias' such as Alzheimer's disease (AD) and movement disorders such as Parkinson's disease (PD). As reviewed elsewhere, in general, these diseases involve progressive neuronal dysfunction over periods of up to a decade or more, usually with eventual loss of neurons or synapses affecting certain specific, vulnerable brain regions earlier and more severely than other regions. There can be substantial overlap between these disease groups. For example, some AD patients develop movement deficits and some patients presenting with PD develop memory impairment and sometimes AD. To some extent this reflects overlap in the regions affected by these disorders but, in part, it is also because, despite different etiologies, neurodegenerative diseases often involve common neurochemical and morphological perturbances, for example changes in cytoskeletal filamentous proteins such as tau or disrupted cell-cell communications (e.g. dendrite pruning, synapse loss). The same broad molecular networks are often involved in the course of neurodegeneration, including mediators of inflammatory or oxidative damage, caspases involved in cell death and, as reviewed here, molecules involved in the re-organisation of the extracellular matrix after cell damage or death. The physical alterations in brain structures that occur when synapses and cells are destroyed in any neurodegenerative disease necessarily entail alterations in the extracellular matrix, so it is not surprising that MMPs alter in several neurodegenerative diseases, including both AD and PD