Synucleinopathies: common features and hippocampal manifestations

Cell Mol Life Sci. 2017 Apr;74(8):1485-1501. doi: 10.1007/s00018-016-2411-y. Epub 2016 Nov 8.


Parkinson's disease (PD), dementia with Lewy Bodies (DLB), and multiple system atrophy (MSA) are three major synucleinopathies characterized by α-synuclein-containing inclusions in the brains of patients. Because the cell types and brain structures that are affected vary markedly between the disorders, the patients have different clinical manifestations in addition to some overlapping symptoms, which are the basis for differential diagnosis. Cognitive impairment and depression associated with hippocampal dysfunction are frequently observed in these disorders. While various α-synuclein-containing inclusions are found in the hippocampal formation, increasing evidence supports that small α-synuclein aggregates or oligomers may be the real culprit, causing deficits in neurotransmission and neurogenesis in the hippocampus and related brain regions, which constitute the major mechanism for the hippocampal dysfunctions and associated neuropsychiatric manifestations in synucleinopathies.

Keywords: Glial cytoplasmic inclusions (GCIs); Glial nuclear inclusions (GNIs); Neuron; Neuronal cytoplasmic inclusions (NCIs); Oligodendrocyte.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Hippocampus / metabolism
  • Hippocampus / pathology*
  • Hippocampus / physiopathology
  • Humans
  • Inclusion Bodies / metabolism
  • Inclusion Bodies / pathology*
  • Lewy Body Disease / metabolism
  • Lewy Body Disease / pathology*
  • Lewy Body Disease / physiopathology
  • Multiple System Atrophy / metabolism
  • Multiple System Atrophy / pathology*
  • Multiple System Atrophy / physiopathology
  • Neurogenesis
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology*
  • Parkinson Disease / physiopathology
  • Protein Aggregates
  • Protein Aggregation, Pathological / metabolism
  • Protein Aggregation, Pathological / pathology
  • Protein Aggregation, Pathological / physiopathology
  • Synaptic Transmission
  • alpha-Synuclein / analysis
  • alpha-Synuclein / metabolism*


  • Protein Aggregates
  • alpha-Synuclein