Acta Neuropathologica

, Volume 129, Issue 3, pp 337–362 | Cite as

Autophagy in neuronal cells: general principles and physiological and pathological functions

  • Markus Damme
  • Taina Suntio
  • Paul Saftig
  • Eeva-Liisa Eskelinen


Autophagy delivers cytoplasmic components and organelles to lysosomes for degradation. This pathway serves to degrade nonfunctional or unnecessary organelles and aggregate-prone and oxidized proteins to produce substrates for energy production and biosynthesis. Macroautophagy delivers large aggregates and whole organelles to lysosomes by first enveloping them into autophagosomes that then fuse with lysosomes. Chaperone-mediated autophagy (CMA) degrades proteins containing the KFERQ-like motif in their amino acid sequence, by transporting them from the cytosol across the lysosomal membrane into the lysosomal lumen. Autophagy is especially important for the survival and homeostasis of postmitotic cells like neurons, because these cells are not able to dilute accumulating detrimental substances and damaged organelles by cell division. Our current knowledge on the autophagic pathways and molecular mechanisms and regulation of autophagy will be summarized in this review. We will describe the physiological functions of macroautophagy and CMA in neuronal cells. Finally, we will summarize the current evidence showing that dysfunction of macroautophagy and/or CMA contributes to neuronal diseases. We will give an overview of our current knowledge on the role of autophagy in aging neurons, and focus on the role of autophagy in four types of neurodegenerative diseases, i.e., amyotrophic lateral sclerosis and frontotemporal dementia, prion diseases, lysosomal storage diseases, and Parkinson’s disease.


Autophagosome Lysosome Chaperone-mediated autophagy Neurogenesis Aging Neurodegeneration FTD/ALS Prion disease Lysosomal storage disease Parkinson’s disease 



ATPase associated with diverse cellular activities


Amyotrophic lateral sclerosis


Activating molecule in beclin 1-regulated autophagy


AMP-activated protein kinase


Activating transcription factor 6




Beclin 1


BCL2/adenovirus E1B 19 kDa interacting protein 3


Charged multivesicular protein 2B


Chaperone-mediated autophagy


Central nervous system


Death-associated protein 1


Double FYVE-containing protein 1


Dorsal root ganglion


Endosomal sorting complex required for transport-III


Endoplasmic reticulum


Extracellular signal-regulated kinase 2


200 kDa FAK family kinase-interacting protein


Frontotemporal dementia


Green fluorescent protein


Guanosine triphosphatase


Hypoxia-inducible factor


Heat shock cognate protein of 70 kDa


Serine/threonine-protein kinase/endoribonuclease protein


Lysosomal associated membrane protein


Microtubule associated protein 1 light chain 3


Leucine-rich repeat kinase 2


Lysosomal storage disorder


Myocyte enhancer factor 2D


Mucolipidosis type II


Neuronal ceroid lipofuscinosis


Niemann–Pick C


Mammalian target of rapamycin


mTOR complex 1


Multivesicular body




Parkinson’s disease


Protein kinase-like ER kinase


Phosphatidyl inositol 3-phosphate


Phosphatidyl inositol 3-kinase class 3


Protein kinase C




Regulatory associated protein of mTOR)


RB1-inducible coiled-coil 1


Repressor element 1 silencing transcription factor


Ras homolog enriched in brain


Reactive oxygen species


Soluble N-ethyl-maleimide-sensitive factor attachment protein receptor


Superoxide dismutase


Sequestosome 1


Tar-DNA binding protein 43


Transcription factor EB


Tuberous sclerosis complex


Ubiquitin-binding domain


Ubiquilin 2


Unc-51-like kinase 1


Unfolded protein response


Vacuolar ATPase


Valosin-containing protein


WD repeat domain, phosphoinositide interacting



Work in the laboratories P.S. and M.D. is supported through Grants of the Deutsche Forschungsgemeinschaft (DFG: SFB877, SPP1580, GRK1459, Cluster of Excellence: Inflammation at Interfaces), the VERUM foundation and the Interuniversity Attraction Poles Program IUAP P7/16 of the Belgian Federal Science Policy Office. E.L.E. and T.S. are supported by the Academy of Finland, Biocentrum Helsinki, and Sigrid Juselius Foundation. We thank Nicolas Yeung (University of Helsinki) for his contribution to designing Fig. 1.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Markus Damme
    • 1
  • Taina Suntio
    • 2
  • Paul Saftig
    • 1
  • Eeva-Liisa Eskelinen
    • 2
  1. 1.Biochemical InstituteUniversity of KielKielGermany
  2. 2.Department of BiosciencesUniversity of HelsinkiHelsinkiFinland

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