Parkinson’s disease (PD) is a progressive neurodegenerative condition with a multifactorial etiology, characterized by dopaminergic neurons being selectively absent in the midbrain. Clinically, PD manifests primarily with core motor symptoms of resting tremor, bradykinesia, and muscle rigidity, and is often accompanied by non-motor symptoms including depression, cognitive impairment, and gastrointestinal dysfunction. Among the extensive relevant research, few have explored the precise pathogenic mechanisms underlying PD, and no curative treatment is available. Current pharmacological therapies mainly provide symptomatic relief by enhancing central dopaminergic function or modulating cholinergic activity; however, their long-term efficacy is frequently constrained by waning therapeutic response, drug tolerance, and adverse reactions. Accumulating evidence suggests that several naturally derived neuroactive compounds—such as gastrodin, uncarin, and paeoniflorin—demonstrate significant potential in combating PD. In this systematic review, we examined original research articles published from 2010 to 2025, retrieved from PubMed, Web of Science, and CNKI databases, using predefined keywords of Parkinson’s disease, neuroprotective herbal compounds, traditional medicine, multi-target mechanisms, natural product, autophagy, neuroinflammation, and oxidative stress. Studies were included if they specifically investigated the mechanistic actions of natural compounds in PD models. Conference abstracts, review articles, publications not in English or Chinese, and studies lacking clearly defined mechanisms were excluded. Analysis of the available literature reveals that natural neuroactive compounds may exert anti-PD effects through multiple mechanisms, e.g., inhibiting pathological α-synuclein aggregation, attenuating neuronal apoptosis, suppressing neuroinflammation, mitigating oxidative stress, and restoring mitochondrial dysfunction. This review provides insights that may inform the clinical application of natural bioactive compounds and guide their further development as potential therapeutic candidates against PD.

Alzheimer’s (AD) and Parkinson’s disease (PD) are prominent neurodegenerative disorders characterized by early synaptic loss, which correlates more closely with clinical symptoms than neuronal death. This synaptic impairment is primarily driven by disruptions in synaptic vesicle (SV) trafficking, a critical process for maintaining synaptic integrity through a tightly regulated cycle involving clustering, docking-priming, Ca²⁺-triggered fusion, and endocytosis. In AD, amyloid-β (Aβ) oligomers interfere with SNARE-mediated fusion and endocytosis, while hyperphosphorylated tau obstructs vesicle mobility and docking, resulting in cumulative toxicity that aggravates SV defects. Conversely, in PD, α-synuclein (α-syn) aggregation alters vesicle clustering, membrane fusion, and recycling, and these effects are further influenced by Leucine-rich repeat kinase 2 (LRRK2)-Rab-related trafficking defects and the selective vulnerability of dopaminergic terminals. Different from previous reviews that address synaptic dysfunction in a broader manner, the present review is specifically organized around the SV trafficking cycle and compares both shared presynaptic endpoints and disease-specific upstream mechanisms in AD and PD. In addition, recent mechanism-oriented therapeutic strategies are summarized. This vesicle-cycle-centered perspective may provide a clearer framework for understanding presynaptic pathology and for guiding the development of earlier and more targeted interventions.

Traumatic brain injury (TBI), a major cause of persistent cognitive impairment (CI), increases the long-term risk of developing dementia, including Alzheimer’s disease (AD). To elucidate this association, we systematically reviewed fluid biomarkers linked to post-TBI cognitive outcomes. A comprehensive search of the PubMed, Embase, and Cochrane Library databases was performed. A total of 29 clinical studies were included, reporting on several biomarkers related to neural injury and repair, AD-like pathology, and inflammation. Among these, neurofilament light chain (NfL), ubiquitin C-terminal hydrolase L1, total tau, and glial fibrillary acidic protein (GFAP) were consistently associated with CI and brain atrophy across various TBI severities and stages. Notably, certain biomarkers assessed during the acute phase (within 7 days post-injury), such as brain-derived neurotrophic factor, neuron-specific enolase, and interleukin-1β, showed significant correlations with CI. In contrast, elevated levels of GFAP and NfL measured during the recovery phase (6 months to 8 years post-injury) were significantly associated with TBI-related CI (TBI-CI). The findings also highlighted that axonal injury, glial activation, neuroinflammation, neuronal damage, and degeneration drive TBI-CI, with tau pathology and synaptic dysfunction emerging as potential bridges from TBI to AD. This review underscores the critical temporal dynamics of fluid biomarkers in TBI-CI, revealing that stage-specific biomarker profiles mirror distinct underlying pathophysiological processes. Future longitudinal studies should focus on well-characterized patient subgroups, adopt standardized diagnostic criteria, and integrate fluid biomarkers with neuroimaging and genetic data.

In the context of the global diabetes epidemic, diabetic nephropathy (DN)—a condition directly associated with diabetes—has become the primary cause of end-stage renal disease, significantly impacting patients’ quality of life and placing substantial demands on public healthcare resources. The pathogenesis of DN is characterized by metabolic disturbances induced by high glucose levels, hemodynamic abnormalities, and the synergistic amplification of various stress signals. These factors collectively contribute to the progressive loss of nephrons and irreversible renal dysfunction. Although current standard treatments can partially slow disease progression, they significantly fail to meet clinical needs. Therefore, there is an urgent necessity to identify multi-target intervention strategies that utilize novel mechanisms of action. Alkaloids, a class of natural nitrogen-containing compounds known for their significant structural diversity, have recently demonstrated multiple renoprotective effects in experimental models of DN. This review is based on a search of the PubMed, Web of Science and CNKI databases. The keywords alkaloids, diabetic nephropathy, diabetic nephropathies, diabetic kidney disease, inflammation, oxidative stress, fibrosis, autophagy and apoptosis were used to search for original research articles in both Chinese and English, published between 2010 and 2026, which investigated the mechanisms by which alkaloid compounds exert their anti-DN effects. Focusing on anti-inflammatory effects, anti-oxidative stress, anti-renal fibrosis, autophagy modulation, apoptosis regulation and ferroptosis inhibition, the review then summarized the relevant literature by systematizing the experimental models, intervention protocols, dosages and key results. This provided a new theoretical perspective and experimental basis for the clinical translation and new drug development of alkaloid compounds for the treatment of DN. The review provides a new theoretical perspective and an experimental basis for the clinical translation of, and new drug development based on, alkaloid compounds for the treatment of DN.