Home › Research › Caregiving
Lysosomal Dysfunction at the Centre of Parkinson's Disease and Frontotemporal Dementia/Amyotrophic Lateral Sclerosis
Wallings RL, Humble SW, Ward ME, Wade-Martins R.. Trends in neurosciences, 2019-11-05
Topic: Brain proteins, microglia and lab models
Parkinson's disease (PD) and frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) are insidious and incurable neurodegenerative diseases that represent a significant burden to affected individuals, caregivers, and an ageing population. Both PD and FTD/ALS are defined at post mortem by the presence of protein aggregates and the loss of specific subsets of neurons. We examine here the crucial role of lysosome dysfunction in these diseases and discuss recent evidence for converging mechanisms. This review draws upon multiple lines of evidence from genetic studies, human tissue, induced pluripotent stem cells (iPSCs), and animal models to argue that lysosomal failure is a primary mechanism of disease, rather than merely reflecting association with protein aggregate end-points. This review provides compelling rationale for targeting lysosomes in future therapeutics for both PD and FTD/ALS.
Key findings
- Parkinson's disease (PD) and frontotemporal dementia/amyotrophic lateral sclerosis (FTD/ALS) are insidious and incurable neurodegenerative diseases that represent a significant burden to affected individuals, caregivers, and an ageing population.
Why it matters
This review argues that lysosomal failure is a primary mechanism in Parkinson's disease and frontotemporal dementia/amyotrophic lateral sclerosis and provides rationale for targeting lysosomes in future therapeutics. It is about other neurodegenerative diseases and does not test any treatment, cure, or prevention for Alzheimer's disease.
New to this subject? Start with our plain-English guide: Caregiving →
Study details
- Evidence strengthLow
How this study scored 47/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Trends in neurosciences) |
| Journal's citation record | 3 / 4 | Trends in Neurosciences: journal h-index 439 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2019 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 144 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 16.0 citations a year over 9 year(s) since 2019 |
| Impact for its field and year | 2 / 6 | Cited 2.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 3 / 4 | Cited 65 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Richard Wade‐Martins: h-index 67 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | National Institutes of Health: institution h-index 2,723 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 31704179) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 47 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Wallings, R. L., Humble, S. W., Ward, M. E., & Wade-Martins, R. (2019). Lysosomal Dysfunction at the Centre of Parkinson's Disease and Frontotemporal Dementia/Amyotrophic Lateral Sclerosis. Trends in neurosciences. https://doi.org/10.1016/j.tins.2019.10.002
Vancouver
Wallings RL, Humble SW, Ward ME, Wade-Martins R. Lysosomal Dysfunction at the Centre of Parkinson's Disease and Frontotemporal Dementia/Amyotrophic Lateral Sclerosis. Trends in neurosciences. 2019. doi:10.1016/j.tins.2019.10.002. PMID: 31704179.
BibTeX
@article{wallings2019-31704179,
author = {Wallings, R. L. and Humble, S. W. and Ward, M. E. and Wade-Martins, R.},
title = {{Lysosomal Dysfunction at the Centre of Parkinson's Disease and Frontotemporal Dementia/Amyotrophic Lateral Sclerosis}},
journal = {Trends in neurosciences},
year = {2019},
doi = {10.1016/j.tins.2019.10.002},
pmid = {31704179},
url = {https://doi.org/10.1016/j.tins.2019.10.002}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Later studies that cite this one
1 study in the alzhub library lists this one in its references.
Related studies in Caregiving
Also tagged “bodies”
1,017 studies in the library carry the topic tag “bodies”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,017 tagged studies.