Synucleinopathies comprise a diverse group of neurodegenerative proteinopathies 
that share common pathological lesions composed of aggregates of conformational 
and posttranslational modifications of alpha-synuclein in selected populations 
of neurons and glia. Abnormal filamentous aggregates of misfolded 
alpha-synuclein protein are the major components of Lewy bodies, dystrophic 
(Lewy) neurites, and the Papp-Lantos filaments in oligodendroglia and neurons in 
multiple system atrophy linked to degeneration of affected brain regions. The 
synucleinopathies include (1) Lewy body disorders and dementia with Lewy bodies, 
(2) multiple system atrophy (MSA), and (3) Hallervorden-Spatz disease. (1) The 
pathological diagnosis of Lewy body disorders and dementia with Lewy bodies is 
established by validated consensus criteria based on semiquantitative assessment 
of subcortical and cortical Lewy bodies as their common hallmarks. They are 
accompanied by subcortical multisystem degeneration with neuronal loss and 
gliosis with or without Alzheimer pathologic state. Lewy bodies also occur in 
numerous other disorders, including pure autonomic failure, neuroaxonal 
dystrophies, and various amyloidoses and tauopathies. (2) Multiple system 
atrophy, a sporadic, adult-onset degenerative movement disorder of unknown 
cause, is characterized by alpha-synuclein-positive glial cytoplasmic and rare 
neuronal inclusions throughout the central nervous system associated with 
striatonigral degeneration, olivopontocerebellar atrophy, and involvement of 
medullar and spinal autonomic nuclei. (3) In neurodegeneration with brain iron 
accumulation type I, or Hallervorden-Spatz disease, alpha-synuclein is present 
in axonal spheroids and glial and neuronal inclusions. While the identity of the 
major components of Lewy bodies suggests that a pathway leading from normal 
soluble to abnormal misfolded filamentous proteins is central for their 
pathogenesis, regardless of the primary disorder, there are conformational 
differences in alpha-synuclein between neuronal and glial aggregates, showing 
nonuniform mapping for its epitopes. Despite several cellular and transgenic 
models, it is not clear whether inclusion body formation is an 
adaptive/neuroprotective or a pathogenic reaction/process generated in response 
to different, mostly undetermined, functional triggers linked to 
neurodegeneration.