Lewy bodies

Abstract

Lewy bodies (LB) in the substantia nigra are a cardinal pathological feature of Parkinson's disease, but they occur in a number of neurodegenerative diseases and can be widespread in the nervous system. The characteristics, locations, and composition of LB are reviewed, with particular attention to ␣-synuclein (␣-SYN), which appears to be the major component of LB. The propensity for ␣-SYN, a presynaptic protein widely expressed in the brain, to aggregate is because of an amyloidogenic central region. The factors that favor the aggregation of ␣-SYN and mechanisms of toxicity are examined, and a mechanism through which aggregates of ␣-SYN could induce mitochondrial dysfunction and͞or release of proapoptotic molecules is proposed.

Depletion of 26S Proteasomes in Mouse Brain Neurons Causes Neurodegeneration and Lewy-Like Inclusions Resembling Human Pale Bodies

“…This could be explained by inherent differences in mechanisms between higher and lower eukaryotes. The formation of inclusion bodies with some of the currently accepted features of Lewy bodies (Shults, 2006) suggests 26S proteasome dysfunction is associated with a cascade of specific neuropathological changes that occur in disease progression.…”

“…5, available at www. jneurosci.org as supplemental material) (data not shown) (Shults, 2006). No A␤ (␤-amyloid)-containing amyloid or tau protein deposits were evident on immunostaining (data not shown).…”

Protein-metal interactions of calmodulin and α-synuclein monitored by selective noncovalent adduct protein probing mass spectrometry

“…␣-Synuclein is the major component of Lewy bodies, (for a comprehensive review, see [14]), which are protein aggregates found in the neuronal and glial cytoplasm of patients affected with Parkinson's disease [15], dementia [16], and a specific variant of Alzheimer's disease [17]. Perhaps the most convincing evi-dence to date that links ␣-synuclein with the onset of Parkinson's disease is the discovery that single point mutations in the gene that codes for ␣-synuclein increases the likelihood of manifesting Parkinson's disease to 85% [18,19].…”

Glucocerebrosidase, a new player changing the old rules in Lewy body diseases

“…The major component of LBs is α -synuclein in the form of amyloid fibrils. However, LBs also contain numerous other proteins and vesicular components (Shults , 2006 ;Wakabayashi et al , 2007 ;Xia et al , 2008 ).…”