Parkinson’s and dementia — are toxins silently destroying the brain?

Aim of the study: SARM1 is a key regulator of a conserved program of axon degeneration increasingly linked to human neurodegenerative diseases. Pathological SARM1 activation causes rapid NAD consumption, disrupting cellular homeostasis and leading to axon degeneration.

Results: In this study, we develop antisense oligonucleotides (ASOs) targeting human SARM1, demonstrating robust neuroprotection against morphological, metabolic, and mitochondrial impairment in human iPSC-derived dopamine neurons induced by the lethal neurotoxin vacor, a potent SARM1 activator. Furthermore, our findings reveal that axon fragmentation can be prevented, and mitochondrial dysfunction reversed using the NAD precursor nicotinamide, a form of vitamin B3, even after SARM1 activation has occurred, when neurons are already unhealthy. This research identifies ASOs as a promising therapeutic strategy to block SARM1, and provides an extensive characterisation and further mechanistic insights that demonstrate the reversibility of SARM1 toxicity in human neurons. It also identifies the SARM1 activator vacor as a specific and reversible neuroablative agent in human neurons.

Aim of the study: The high prevalence of neurodegenerative diseases is an unintended consequence of the high longevity of the population, together with the lack of effective preventive and therapeutic options. There is great pressure on preclinical research, and both old and new models of neurodegenerative diseases are required to increase the pipeline of new drugs for clinical testing.

Results: Several agents have been used to model neuroinflammation-based neurodegeneration and dementia in AD, including lipopolysaccharide (LPS), streptozotocin, and monomeric C-reactive protein. The bacterial agent LPS makes a useful rodent model for testing anti-inflammatory therapies to halt the development and severity of AD. However, neurotoxin models might be more useful than genetic models for drug discovery in PD but that is not the case in AD where they cannot beat the new developments in transgenic mouse models. Overall, we should work using all available models, either in vivo, in vitro, or in silico, considering the seriousness of the moment and urgency of developing effective drugs.

Aim of the study: In the last few years, neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD) have attracted attention due to their high prevalence worldwide. Environmental factors may be one of the biggest reasons for these diseases related to neuronal dysfunctions.

Results: Some of the neurotoxic metals such as lead, aluminum, mercury, manganese, cadmium, and arsenic as well as some pesticides and metal-based nanoparticles have been involved in AD and PD due to their ability to produce senile/amyloid plaques and NFTs which are the main feature of these neuronal dysfunctions. Exposure to solvents is also majorly responsible for neurodegenerative disorders. The present review highlights the impact of omnipresent heavy metals with some other neurotoxins on human health and how they give rise to neuronal dysfunctions which in turn causes socio-economic consequences due to increasing pollution worldwide. Graphical abstract.

Aim of the study: The world is suffering a pandemic of neurodevelopment and neurodegenerative disorders. Autism, attention-deficit/hyperactivity disorder, dementia, Alzheimer disease, Parkinson disease-the list is long-have all increased relentlessly the past few decades.

Results: The world is suffering a pandemic of neurodevelopment and neurodegenerative disorders. Autism, attention-deficit/hyperactivity disorder, dementia, Alzheimer disease, Parkinson disease-the list is long-have all increased relentlessly the past few decades. The primary cause appears to be the saturation of the environment with microbial, chemical, and metal neurotoxins. This editorial reviews the research on commonly found neurotoxins and attempts to assess their contribution to neurodegeneration and its prevalence in the population.

Aim of the study: Heavy metals and metalloids are persistent environmental contaminants that accumulate in the central nervous system and interact with endogenous essential metals, yet most neurotoxicological research continues to treat metals as independent agents rather than as co-occurring mixtures.

Results: Following a PubMed search (January 2016-June 2026), 93 unique studies were included (AD: 49; PD: 38; ALS: 19; MS: 18; 31 shared across diseases). Combined exposure to lead, cadmium, arsenic, and mercury is linked to amyloid-beta accumulation and dementia risk in AD; manganese-vanadium co-exposure produces more severe dopaminergic damage in PD than either metal alone, with manganese activating the familial PD gene LRRK2; a multi-metal mixture in ALS was associated with a three-fold higher disease risk independent of genetic susceptibility; and MS showed almost no designed mixture studies despite considerable single-metal data, with conflicting findings across cohorts. Three general mechanisms were identified: competition at shared membrane transporters (notably DMT1), sequestration by metal-binding proteins, and direct synergistic or antagonistic interactions, in which essential elements can modulate toxic-metal handling.