Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities

Fiona M. Menzies; Angeleen Fleming; Andrea Caricasole; Carla F. Bento; Stephen P. Andrews; Avraham Ashkenazi; Jens Füllgrabe; Anne Jackson; Maria Jimenez Sanchez; Cansu Karabiyik; Floriana Licitra; Ana Lopez Ramirez; Mariana Pavel; Claudia Puri; Maurizio Renna; Thomas Ricketts; Lars Schlotawa; Mariella Vicinanza; Hyeran Won; Ye Zhu; John Skidmore; David C. Rubinsztein

doi:10.1016/j.neuron.2017.01.022

Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities

Fiona M. Menzies, Angeleen Fleming, Andrea Caricasole, Carla F. Bento, Stephen P. Andrews, Avraham Ashkenazi, Jens Füllgrabe, Anne Jackson, Maria Jimenez Sanchez, Cansu Karabiyik, Floriana Licitra, Ana Lopez Ramirez, Mariana Pavel, Claudia Puri, Maurizio Renna, Thomas Ricketts, Lars Schlotawa, Mariella Vicinanza, Hyeran Won, Ye ZhuJohn Skidmore, David C. Rubinsztein^*

^*Corresponding author for this work

Basic and Clinical Neuroscience

Research output: Contribution to journal › Review article › peer-review

821 Citations (Scopus)

Abstract

Autophagy is a conserved pathway that delivers cytoplasmic contents to the lysosome for degradation. Here we consider its roles in neuronal health and disease. We review evidence from mouse knockout studies demonstrating the normal functions of autophagy as a protective factor against neurodegeneration associated with intracytoplasmic aggregate-prone protein accumulation as well as other roles, including in neuronal stem cell differentiation. We then describe how autophagy may be affected in a range of neurodegenerative diseases. Finally, we describe how autophagy upregulation may be a therapeutic strategy in a wide range of neurodegenerative conditions and consider possible pathways and druggable targets that may be suitable for this objective.

Original language	English
Pages (from-to)	1015-1034
Number of pages	20
Journal	Neuron
Volume	93
Issue number	5
Early online date	8 Mar 2017
DOIs	https://doi.org/10.1016/j.neuron.2017.01.022
Publication status	Published - 8 Mar 2017

Keywords

Alzheimer's disease
autophagy
dementia
Huntington's disease
lysosome
motor neuron disease
neurodegeneration
Parkinson's disease
tau

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Menzies, F. M., Fleming, A., Caricasole, A., Bento, C. F., Andrews, S. P., Ashkenazi, A., Füllgrabe, J., Jackson, A., Jimenez Sanchez, M., Karabiyik, C., Licitra, F., Lopez Ramirez, A., Pavel, M., Puri, C., Renna, M., Ricketts, T., Schlotawa, L., Vicinanza, M., Won, H., ... Rubinsztein, D. C. (2017). Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities. Neuron, 93(5), 1015-1034. https://doi.org/10.1016/j.neuron.2017.01.022

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title = "Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities",

abstract = "Autophagy is a conserved pathway that delivers cytoplasmic contents to the lysosome for degradation. Here we consider its roles in neuronal health and disease. We review evidence from mouse knockout studies demonstrating the normal functions of autophagy as a protective factor against neurodegeneration associated with intracytoplasmic aggregate-prone protein accumulation as well as other roles, including in neuronal stem cell differentiation. We then describe how autophagy may be affected in a range of neurodegenerative diseases. Finally, we describe how autophagy upregulation may be a therapeutic strategy in a wide range of neurodegenerative conditions and consider possible pathways and druggable targets that may be suitable for this objective.",

keywords = "Alzheimer's disease, autophagy, dementia, Huntington's disease, lysosome, motor neuron disease, neurodegeneration, Parkinson's disease, tau",

author = "Menzies, {Fiona M.} and Angeleen Fleming and Andrea Caricasole and Bento, {Carla F.} and Andrews, {Stephen P.} and Avraham Ashkenazi and Jens F{\"u}llgrabe and Anne Jackson and {Jimenez Sanchez}, Maria and Cansu Karabiyik and Floriana Licitra and {Lopez Ramirez}, Ana and Mariana Pavel and Claudia Puri and Maurizio Renna and Thomas Ricketts and Lars Schlotawa and Mariella Vicinanza and Hyeran Won and Ye Zhu and John Skidmore and Rubinsztein, {David C.}",

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doi = "10.1016/j.neuron.2017.01.022",

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Menzies, FM, Fleming, A, Caricasole, A, Bento, CF, Andrews, SP, Ashkenazi, A, Füllgrabe, J, Jackson, A, Jimenez Sanchez, M, Karabiyik, C, Licitra, F, Lopez Ramirez, A, Pavel, M, Puri, C, Renna, M, Ricketts, T, Schlotawa, L, Vicinanza, M, Won, H, Zhu, Y, Skidmore, J & Rubinsztein, DC 2017, 'Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities', Neuron, vol. 93, no. 5, pp. 1015-1034. https://doi.org/10.1016/j.neuron.2017.01.022

TY - JOUR

T1 - Autophagy and Neurodegeneration

T2 - Pathogenic Mechanisms and Therapeutic Opportunities

AU - Menzies, Fiona M.

AU - Fleming, Angeleen

AU - Caricasole, Andrea

AU - Bento, Carla F.

AU - Andrews, Stephen P.

AU - Ashkenazi, Avraham

AU - Füllgrabe, Jens

AU - Jackson, Anne

AU - Jimenez Sanchez, Maria

AU - Karabiyik, Cansu

AU - Licitra, Floriana

AU - Lopez Ramirez, Ana

AU - Pavel, Mariana

AU - Puri, Claudia

AU - Renna, Maurizio

AU - Ricketts, Thomas

AU - Schlotawa, Lars

AU - Vicinanza, Mariella

AU - Won, Hyeran

AU - Zhu, Ye

AU - Skidmore, John

AU - Rubinsztein, David C.

PY - 2017/3/8

Y1 - 2017/3/8

N2 - Autophagy is a conserved pathway that delivers cytoplasmic contents to the lysosome for degradation. Here we consider its roles in neuronal health and disease. We review evidence from mouse knockout studies demonstrating the normal functions of autophagy as a protective factor against neurodegeneration associated with intracytoplasmic aggregate-prone protein accumulation as well as other roles, including in neuronal stem cell differentiation. We then describe how autophagy may be affected in a range of neurodegenerative diseases. Finally, we describe how autophagy upregulation may be a therapeutic strategy in a wide range of neurodegenerative conditions and consider possible pathways and druggable targets that may be suitable for this objective.

AB - Autophagy is a conserved pathway that delivers cytoplasmic contents to the lysosome for degradation. Here we consider its roles in neuronal health and disease. We review evidence from mouse knockout studies demonstrating the normal functions of autophagy as a protective factor against neurodegeneration associated with intracytoplasmic aggregate-prone protein accumulation as well as other roles, including in neuronal stem cell differentiation. We then describe how autophagy may be affected in a range of neurodegenerative diseases. Finally, we describe how autophagy upregulation may be a therapeutic strategy in a wide range of neurodegenerative conditions and consider possible pathways and druggable targets that may be suitable for this objective.

KW - Alzheimer's disease

KW - autophagy

KW - dementia

KW - Huntington's disease

KW - lysosome

KW - motor neuron disease

KW - neurodegeneration

KW - Parkinson's disease

KW - tau

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U2 - 10.1016/j.neuron.2017.01.022

DO - 10.1016/j.neuron.2017.01.022

M3 - Review article

C2 - 28279350

AN - SCOPUS:85014799386

SN - 0896-6273

VL - 93

SP - 1015

EP - 1034

JO - Neuron

JF - Neuron

IS - 5

ER -

Autophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities

Abstract

Keywords

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