---
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>. Elsevier. <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>. Elsevier, 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. Elsevier, 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, Elsevier, 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: 2025-12-29T13:47:58Z
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
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  creator: dernst
  date_created: 2025-12-29T13:47:27Z
  date_updated: 2025-12-29T13:47:27Z
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  file_size: 327847
  relation: main_file
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file_date_updated: 2025-12-29T13:47:27Z
has_accepted_license: '1'
intvolume: '        48'
isi: 1
issue: '9'
language:
- iso: eng
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: Elsevier
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
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'
...