---
OA_place: publisher
OA_type: hybrid
PlanS_conform: '1'
_id: '20154'
abstract:
- lang: eng
  text: In long-lived mammals, including humans, brain cell homeostasis is critical
    for maintaining brain function throughout life. Most neurons are generated during
    development and must maintain their cellular identity and plasticity to preserve
    brain function. Although extensive studies indicate the importance of recycling
    and regenerating cellular molecules to maintain cellular homeostasis, recent evidence
    has shown that some proteins and RNAs do not turn over for months and even years.
    We propose that these long-lived cellular molecules may be the basis for maintaining
    brain function in the long term, but also a potential convergent target of brain
    aging. We highlight key discoveries and challenges, and propose potential directions
    to unravel the mystery of brain cell longevity.
acknowledgement: The work was supported by the Deutsche Forschungsgemeinschaft (DFG,
  German Research Foundation) (470322152 – T1347/3-1; 497658532 – T1347/4-1; 507965872
  – T1347/5-1; and 460333672 – CRC1540 Exploring Brain Mechanics) to T.T., the Schram
  Foundation (T.T.), the European Research Council (ERC-2018-STG, 804468 EAGER; ERC-2023-COG,
  101125034 NEUTIME) to T.T., the Hans-Georg Geis und Xue Hong Dong-Geis Foundation
  and Forschungsstiftung Medizin am Universitätsklinikum Erlangen to T.T., and the
  Interdisciplinary Centre for Clinical Research Erlangen (Interdisziplinäres Zentrum
  für Klinische Forschung, Universitätsklinikum Erlangen; P162 to T.T.). We thank
  Dr Laura J. Harrison for editing assistance.
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Martin W
  full_name: Hetzer, Martin W
  id: 86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed
  last_name: Hetzer
  orcid: 0000-0002-2111-992X
- first_name: Tomohisa
  full_name: Toda, Tomohisa
  last_name: Toda
citation:
  ama: Hetzer M, Toda T. Long-lived cellular molecules in the brain. <i>Trends in
    Neurosciences</i>. 2025;48(9):645-654. doi:<a href="https://doi.org/10.1016/j.tins.2025.07.004">10.1016/j.tins.2025.07.004</a>
  apa: Hetzer, M., &#38; Toda, T. (2025). Long-lived cellular molecules in the brain.
    <i>Trends in Neurosciences</i>. Cell Press. <a href="https://doi.org/10.1016/j.tins.2025.07.004">https://doi.org/10.1016/j.tins.2025.07.004</a>
  chicago: Hetzer, Martin, and Tomohisa Toda. “Long-Lived Cellular Molecules in the
    Brain.” <i>Trends in Neurosciences</i>. Cell Press, 2025. <a href="https://doi.org/10.1016/j.tins.2025.07.004">https://doi.org/10.1016/j.tins.2025.07.004</a>.
  ieee: M. Hetzer and T. Toda, “Long-lived cellular molecules in the brain,” <i>Trends
    in Neurosciences</i>, vol. 48, no. 9. Cell Press, pp. 645–654, 2025.
  ista: Hetzer M, Toda T. 2025. Long-lived cellular molecules in the brain. Trends
    in Neurosciences. 48(9), 645–654.
  mla: Hetzer, Martin, and Tomohisa Toda. “Long-Lived Cellular Molecules in the Brain.”
    <i>Trends in Neurosciences</i>, vol. 48, no. 9, Cell Press, 2025, pp. 645–54,
    doi:<a href="https://doi.org/10.1016/j.tins.2025.07.004">10.1016/j.tins.2025.07.004</a>.
  short: M. Hetzer, T. Toda, Trends in Neurosciences 48 (2025) 645–654.
corr_author: '1'
date_created: 2025-08-10T22:01:29Z
date_published: 2025-09-01T00:00:00Z
date_updated: 2026-10-20T08:54:50Z
day: '01'
ddc:
- '570'
department:
- _id: MaHe
doi: 10.1016/j.tins.2025.07.004
external_id:
  isi:
  - '001568965400001'
  pmid:
  - '40744775'
file:
- access_level: open_access
  checksum: 90942491b499f70b0bf48b8aec2e7387
  content_type: application/pdf
  creator: dernst
  date_created: 2025-12-29T13:47:27Z
  date_updated: 2025-12-29T13:47:27Z
  file_id: '20873'
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  file_size: 327847
  relation: main_file
  success: 1
file_date_updated: 2025-12-29T13:47:27Z
fulldoi: https://doi.org/10.1016/j.tins.2025.07.004
has_accepted_license: '1'
intvolume: '        48'
isi: 1
issue: '9'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '09'
oa: 1
oa_version: Published Version
page: 645-654
pmid: 1
publication: Trends in Neurosciences
publication_identifier:
  eissn:
  - 1878-108X
  issn:
  - 0166-2236
publication_status: published
publisher: Cell Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Long-lived cellular molecules in the brain
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 48
year: '2025'
...
---
_id: '7957'
abstract:
- lang: eng
  text: "Neurodevelopmental disorders (NDDs) are a class of disorders affecting brain
    development and function and are characterized by wide genetic and clinical variability.
    In this review, we discuss the multiple factors that influence the clinical presentation
    of NDDs, with particular attention to gene vulnerability, mutational load, and
    the two-hit model. Despite the complex architecture of\r\nmutational events associated
    with NDDs, the various proteins involved appear to converge on common pathways,
    such as synaptic plasticity/function, chromatin remodelers and the mammalian target
    of rapamycin (mTOR) pathway. A thorough understanding of the mechanisms behind
    these pathways will hopefully lead to the identification of candidates that could
    be targeted for treatment approaches."
acknowledgement: We wish to thank Jasmin Morandell for generously sharing Figure 2.
  This work was supported by the European Research Council Starting Grant (grant 715508
  ) to G.N.
article_processing_charge: No
article_type: original
author:
- first_name: Ilaria
  full_name: Parenti, Ilaria
  id: D93538B0-5B71-11E9-AC62-02EBE5697425
  last_name: Parenti
- first_name: Luis E
  full_name: Garcia Rabaneda, Luis E
  id: 33D1B084-F248-11E8-B48F-1D18A9856A87
  last_name: Garcia Rabaneda
- first_name: Hanna
  full_name: Schön, Hanna
  id: C8E17EDC-D7AA-11E9-B7B7-45ECE5697425
  last_name: Schön
- first_name: Gaia
  full_name: Novarino, Gaia
  id: 3E57A680-F248-11E8-B48F-1D18A9856A87
  last_name: Novarino
  orcid: 0000-0002-7673-7178
citation:
  ama: 'Parenti I, Garcia Rabaneda LE, Schön H, Novarino G. Neurodevelopmental disorders:
    From genetics to functional pathways. <i>Trends in Neurosciences</i>. 2020;43(8):608-621.
    doi:<a href="https://doi.org/10.1016/j.tins.2020.05.004">10.1016/j.tins.2020.05.004</a>'
  apa: 'Parenti, I., Garcia Rabaneda, L. E., Schön, H., &#38; Novarino, G. (2020).
    Neurodevelopmental disorders: From genetics to functional pathways. <i>Trends
    in Neurosciences</i>. Elsevier. <a href="https://doi.org/10.1016/j.tins.2020.05.004">https://doi.org/10.1016/j.tins.2020.05.004</a>'
  chicago: 'Parenti, Ilaria, Luis E Garcia Rabaneda, Hanna Schön, and Gaia Novarino.
    “Neurodevelopmental Disorders: From Genetics to Functional Pathways.” <i>Trends
    in Neurosciences</i>. Elsevier, 2020. <a href="https://doi.org/10.1016/j.tins.2020.05.004">https://doi.org/10.1016/j.tins.2020.05.004</a>.'
  ieee: 'I. Parenti, L. E. Garcia Rabaneda, H. Schön, and G. Novarino, “Neurodevelopmental
    disorders: From genetics to functional pathways,” <i>Trends in Neurosciences</i>,
    vol. 43, no. 8. Elsevier, pp. 608–621, 2020.'
  ista: 'Parenti I, Garcia Rabaneda LE, Schön H, Novarino G. 2020. Neurodevelopmental
    disorders: From genetics to functional pathways. Trends in Neurosciences. 43(8),
    608–621.'
  mla: 'Parenti, Ilaria, et al. “Neurodevelopmental Disorders: From Genetics to Functional
    Pathways.” <i>Trends in Neurosciences</i>, vol. 43, no. 8, Elsevier, 2020, pp.
    608–21, doi:<a href="https://doi.org/10.1016/j.tins.2020.05.004">10.1016/j.tins.2020.05.004</a>.'
  short: I. Parenti, L.E. Garcia Rabaneda, H. Schön, G. Novarino, Trends in Neurosciences
    43 (2020) 608–621.
corr_author: '1'
date_created: 2020-06-14T22:00:49Z
date_published: 2020-08-01T00:00:00Z
date_updated: 2026-04-02T14:36:06Z
day: '01'
ddc:
- '570'
department:
- _id: GaNo
doi: 10.1016/j.tins.2020.05.004
ec_funded: 1
external_id:
  isi:
  - '000553090600008'
  pmid:
  - '32507511'
file:
- access_level: open_access
  checksum: 67db0251b1d415ae59005f876fcf9e34
  content_type: application/pdf
  creator: dernst
  date_created: 2020-11-25T09:43:40Z
  date_updated: 2020-11-25T09:43:40Z
  file_id: '8805'
  file_name: 2020_TrendsNeuroscience_Parenti.pdf
  file_size: 1439550
  relation: main_file
  success: 1
file_date_updated: 2020-11-25T09:43:40Z
fulldoi: https://doi.org/10.1016/j.tins.2020.05.004
has_accepted_license: '1'
intvolume: '        43'
isi: 1
issue: '8'
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
page: 608-621
pmid: 1
project:
- _id: 25444568-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '715508'
  name: Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo
    and in vitro Models
publication: Trends in Neurosciences
publication_identifier:
  eissn:
  - 1878-108X
  issn:
  - 0166-2236
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: '1'
status: public
title: 'Neurodevelopmental disorders: From genetics to functional pathways'
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
volume: 43
year: '2020'
...
---
OA_type: closed access
_id: '3805'
abstract:
- lang: eng
  text: The operation of neuronal networks crucially depends on a fast time course
    of signaling in inhibitory interneurons. Synapses that excite interneurons generate
    fast currents, owing to the expression of glutamate receptors of specific subunit
    composition. Interneurons generate brief action potentials in response to transient
    synaptic activation and discharge repetitively at very high frequencies during
    sustained stimulation. The ability to generate short-duration action potentials
    at high frequencies depends on the expression of specific voltage-gated K+ channels.
    Factors facilitating fast action potential initiation following synaptic excitation
    include depolarized interneuron resting potential, subthreshold conductances and
    active dendrites. Finally, GABA release at interneuron output synapses is rapid
    and highly synchronized, leading to a faster inhibition in postsynaptic interneurons
    than in principal cells. Thus, the expression of distinct transmitter receptors
    and voltage-gated ion channels ensures that interneurons operate with high speed
    and temporal precision.
article_processing_charge: No
article_type: original
author:
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
- first_name: Josef
  full_name: Bischofberger, Josef
  last_name: Bischofberger
- first_name: Desdemona
  full_name: Fricker, Desdemona
  last_name: Fricker
- first_name: Richard
  full_name: Miles, Richard
  last_name: Miles
citation:
  ama: 'Jonas PM, Bischofberger J, Fricker D, Miles R. Interneuron Diversity series:
    Fast in, fast out--temporal and spatial signal processing in hippocampal interneurons.
    <i>Trends in Neurosciences</i>. 2004;27(1):30-40. doi:<a href="https://doi.org/doi:10.1016/j.tins.2003.10.010">doi:10.1016/j.tins.2003.10.010</a>'
  apa: 'Jonas, P. M., Bischofberger, J., Fricker, D., &#38; Miles, R. (2004). Interneuron
    Diversity series: Fast in, fast out--temporal and spatial signal processing in
    hippocampal interneurons. <i>Trends in Neurosciences</i>. Elsevier. <a href="https://doi.org/doi:10.1016/j.tins.2003.10.010">https://doi.org/doi:10.1016/j.tins.2003.10.010</a>'
  chicago: 'Jonas, Peter M, Josef Bischofberger, Desdemona Fricker, and Richard Miles.
    “Interneuron Diversity Series: Fast in, Fast out--Temporal and Spatial Signal
    Processing in Hippocampal Interneurons.” <i>Trends in Neurosciences</i>. Elsevier,
    2004. <a href="https://doi.org/doi:10.1016/j.tins.2003.10.010">https://doi.org/doi:10.1016/j.tins.2003.10.010</a>.'
  ieee: 'P. M. Jonas, J. Bischofberger, D. Fricker, and R. Miles, “Interneuron Diversity
    series: Fast in, fast out--temporal and spatial signal processing in hippocampal
    interneurons,” <i>Trends in Neurosciences</i>, vol. 27, no. 1. Elsevier, pp. 30–40,
    2004.'
  ista: 'Jonas PM, Bischofberger J, Fricker D, Miles R. 2004. Interneuron Diversity
    series: Fast in, fast out--temporal and spatial signal processing in hippocampal
    interneurons. Trends in Neurosciences. 27(1), 30–40.'
  mla: 'Jonas, Peter M., et al. “Interneuron Diversity Series: Fast in, Fast out--Temporal
    and Spatial Signal Processing in Hippocampal Interneurons.” <i>Trends in Neurosciences</i>,
    vol. 27, no. 1, Elsevier, 2004, pp. 30–40, doi:<a href="https://doi.org/doi:10.1016/j.tins.2003.10.010">doi:10.1016/j.tins.2003.10.010</a>.'
  short: P.M. Jonas, J. Bischofberger, D. Fricker, R. Miles, Trends in Neurosciences
    27 (2004) 30–40.
date_created: 2018-12-11T12:05:16Z
date_published: 2004-01-01T00:00:00Z
date_updated: 2026-09-11T10:25:02Z
day: '01'
doi: doi:10.1016/j.tins.2003.10.010
extern: '1'
external_id:
  pmid:
  - '14698608'
fulldoi: https://doi.org/doi:10.1016/j.tins.2003.10.010
intvolume: '        27'
issue: '1'
language:
- iso: eng
month: '01'
oa_version: None
page: 30 - 40
pmid: 1
publication: Trends in Neurosciences
publication_identifier:
  eissn:
  - 1878-108X
  issn:
  - 0166-2236
publication_status: published
publisher: Elsevier
publist_id: '2404'
status: public
title: 'Interneuron Diversity series: Fast in, fast out--temporal and spatial signal
  processing in hippocampal interneurons'
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 27
year: '2004'
...
---
OA_type: closed access
_id: '3142'
article_processing_charge: No
author:
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
- first_name: Ina
  full_name: Kramer, Ina
  last_name: Kramer
- first_name: Silvia
  full_name: Arber, Silvia
  last_name: Arber
citation:
  ama: 'Hippenmeyer S, Kramer I, Arber S. Control of neuronal phenotype: What targets
    tell the cell bodies. <i>Trends in Neurosciences</i>. 2004;27(8):482-488. doi:<a
    href="https://doi.org/10.1016/j.tins.2004.05.012">10.1016/j.tins.2004.05.012</a>'
  apa: 'Hippenmeyer, S., Kramer, I., &#38; Arber, S. (2004). Control of neuronal phenotype:
    What targets tell the cell bodies. <i>Trends in Neurosciences</i>. Elsevier. <a
    href="https://doi.org/10.1016/j.tins.2004.05.012">https://doi.org/10.1016/j.tins.2004.05.012</a>'
  chicago: 'Hippenmeyer, Simon, Ina Kramer, and Silvia Arber. “Control of Neuronal
    Phenotype: What Targets Tell the Cell Bodies.” <i>Trends in Neurosciences</i>.
    Elsevier, 2004. <a href="https://doi.org/10.1016/j.tins.2004.05.012">https://doi.org/10.1016/j.tins.2004.05.012</a>.'
  ieee: 'S. Hippenmeyer, I. Kramer, and S. Arber, “Control of neuronal phenotype:
    What targets tell the cell bodies,” <i>Trends in Neurosciences</i>, vol. 27, no.
    8. Elsevier, pp. 482–488, 2004.'
  ista: 'Hippenmeyer S, Kramer I, Arber S. 2004. Control of neuronal phenotype: What
    targets tell the cell bodies. Trends in Neurosciences. 27(8), 482–488.'
  mla: 'Hippenmeyer, Simon, et al. “Control of Neuronal Phenotype: What Targets Tell
    the Cell Bodies.” <i>Trends in Neurosciences</i>, vol. 27, no. 8, Elsevier, 2004,
    pp. 482–88, doi:<a href="https://doi.org/10.1016/j.tins.2004.05.012">10.1016/j.tins.2004.05.012</a>.'
  short: S. Hippenmeyer, I. Kramer, S. Arber, Trends in Neurosciences 27 (2004) 482–488.
date_created: 2018-12-11T12:01:38Z
date_published: 2004-08-01T00:00:00Z
date_updated: 2026-09-17T12:46:45Z
day: '01'
doi: 10.1016/j.tins.2004.05.012
extern: '1'
external_id:
  pmid:
  - '15271496'
fulldoi: https://doi.org/10.1016/j.tins.2004.05.012
intvolume: '        27'
issue: '8'
language:
- iso: eng
month: '08'
oa_version: None
page: 482 - 488
pmid: 1
publication: Trends in Neurosciences
publication_identifier:
  eissn:
  - 1878-108X
  issn:
  - 0166-2236
publication_status: published
publisher: Elsevier
publist_id: '3555'
status: public
title: 'Control of neuronal phenotype: What targets tell the cell bodies'
type: review
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 27
year: '2004'
...