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Role of Autophagy in Brain Sculpture: Physiological and Pathological Implications

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Autophagy Networks in Inflammation

Part of the book series: Progress in Inflammation Research ((PIR))

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Abstract

The brain has the ability to change during the life rearranging itself by the elimination and the formation of new connections between neurons. This dynamic capacity is known as brain plasticity or neuroplasticity, and is associated with functional changes involving functional recovery after brain damage, learning, memory, and addiction. It is well defined that protein synthesis is required for neuroplasticity and the establishment of long-term memories, but protein degradation plays also a crucial role in neuronal physiology and pathology. Ubiquitin-proteasome system, which degrades short-lived proteins, is important in synaptic plasticity, learning and memory, as well as lysosome system, which involves endocytosis to degrade proteins, plays a role in synaptic plasticity regulating receptor trafficking. The third major degradation pathway is the autophagy which degrades long-lived cytoplasmic proteins or damaged organelles to maintain normal cell homeostasis. Recent evidence suggests the involvement of autophagy in synaptic plasticity, in addition to its crucial role in the quality control of proteins and organelles in neurons. Thus an impairment of the autophagic machinery is closely connected with the alteration of neuronal function and neuron ability to respond to damage. A clear understanding of neuronal autophagy in brain physiology and pathology could help to develop new pharmaceutical approaches for the treatment of neurological disorders. The current Chapter will focus on the key role of autophagy in the development and function of the central nervous system (CNS), and on the emerging evidence of autophagy deregulation in neurodegenerative disease and acute brain damage.

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Abbreviations

3-MA:

3-methyladenine

AD:

Alzheimer’s Disease

Akt (PKB):

Protein kinase B

Ambra1:

Autophagy/Beclin-1 Regulator 1

AMPAR:

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor

APP:

Amyloid precursor protein

ASD:

Autism spectrum disorders

Atg:

Autophagy-related

ATP:

Adenosine triphosphate

AVs:

Autophagic vacuoles

Aβ:

β-amyloid peptide

Bcl-2:

B-cell lymphoma 2

Bcl-XL:

B-cell lymphoma-extra large

Bif-1:

BAX-interacting factor-1

Bim:

B-cell lymphoma 2 interacting mediator of cell death

CCI:

Controlled cortical impact injury

CIII PI3K:

Class III phosphatidylinositol 3-kinase

CMA:

Chaperone-mediated autophagy

CNS:

Central nervous system

COMT:

Catechol-o-methyltransferase

Deptor:

DEP domain containing MTOR-interacting protein

ER:

Endoplasmic reticulum

FAD:

Familial AD

Fbxo7:

F-box protein 7

FIP200:

FAK Family Kinase-Interacting Protein of 200 kDa

FPI:

Fluid percussion injury

GABAA,:

γ-aminobutyric acid

GCEE:

γ-glutamylcysteinyl ethyl ester

H/I:

Hypoxia/ischemia

HCb:

Hemicerebellectomy

HD:

Huntington’s disease

HDAC6:

Histone deacetylase 6

Htt:

Huntingtin

i.c.v.:

Intracerebroventricular

IO:

Inferior olive

IRGM:

Immune-related GTPase M

KO:

Knockout

LAMP:

Lysosome-associated membrane protein type

LC3:

Microtubule-associated protein 1 light chain 3

LRRK2:

Leucine-rich repeat kinase 2

LTD:

Long-term depression

LTP:

Long-term potentiation

MAO-B:

Monoamine oxidase B

Mfn1:

Mitofusin 1

MPP+:

1-methyl-4-phenylpyridinium

mTOR:

Mammalian target of rapamycin

mTORC1:

mTOR complex 1

NBR1:

Neighbor Of BRCA1 Gene 1

Ndp52:

Nuclear dot protein 52 kDa

NGF:

Nerve growth factor

NMDAR:

N-methyl-d-aspartate receptor

NPCs:

Neural progenitor cells

NSF:

N-ethylmaleimide-sensitive factor

p62/SQSTM1:

Sequestosome 1

PD:

Parkinson’s Disease

PE:

Phosphatidylethanolamine

PI3K:

Phosphatidylinositol 3-kinase

PI3P:

Phosphatidylinositol 3-phosphate

PINK1:

PTEN-induced putative kinase 1

pMCAO:

Permanent middle cerebral artery occlusion

Pn:

Pontine nuclei

polyQ:

Polyglutamine

PP1:

Protein phosphatase 1

PRAS40:

Proline-rich Akt substrate of 40 kDa

PSD95:

Postsynaptic density protein 95

PSEN:

Presenilin

PTEN:

Phosphatase and tensin homolog

Raptor:

Regulatory-associated protein of mTOR

Rubicon:

RUN and cysteine rich domain containing beclin 1 interacting protein

SCI:

Spinal cord injury

SVZ:

Subventricular zone

TBI:

Traumatic brain injury

tMCAO:

Transient middle cerebral artery occlusion

TrkA:

Tropomyosin receptor kinase A

Tsc2:

Tuberous sclerosis proteins

ULK1:

UNC-51-like kinase 1

UVRAG:

UV Radiation Resistance-Associated Gene

VDAC1:

Voltage-dependent anion channel 1

VMP1:

Vacuole Membrane Protein 1

WIPI-1:

WD-repeat protein Interacting with PhosphoInositides-1

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  1. Department of Medicine, University Campus-Biomedico, Via Alvaro del Portillo, 21, Rome, Italy

    Annalisa Nobili & Marcello D’Amelio

  2. Department of Experimental Neurosciences, IRCCS S. Lucia Foundation, Rome, Italy

    Annalisa Nobili & Marcello D’Amelio

  3. Department of Experimental Neurosciences, IRCCS S. Lucia Foundation, Via del Fosso di Fiorano, 64, Rome, Italy

    Virve Cavallucci

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  1. Annalisa Nobili
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  1. Centre de Recherche des Cordeliers, UMRS 1138 – Team 11,, Paris, France

    Maria Chiara Maiuri

  2. Multi Medica Fondazione Onlus, Milan, Italy

    Daniela De Stefano

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Nobili, A., Cavallucci, V., D’Amelio, M. (2016). Role of Autophagy in Brain Sculpture: Physiological and Pathological Implications. In: Maiuri, M., De Stefano, D. (eds) Autophagy Networks in Inflammation. Progress in Inflammation Research. Springer, Cham. https://doi.org/10.1007/978-3-319-30079-5_11

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